27 results on '"Hirst CS"'
Search Results
2. Kif1bp loss in mice leads to defects in the peripheral and central nervous system and perinatal death
- Author
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Hirst, CS, Stamp, LA, Bergner, AJ, Hao, MM, Tran, MX, Morgan, JM, Dutschmann, M, Allen, AM, Paxinos, G, Furlong, TM, McKeown, SJ, Young, HM, Hirst, CS, Stamp, LA, Bergner, AJ, Hao, MM, Tran, MX, Morgan, JM, Dutschmann, M, Allen, AM, Paxinos, G, Furlong, TM, McKeown, SJ, and Young, HM
- Abstract
Goldberg-Shprintzen syndrome is a poorly understood condition characterized by learning difficulties, facial dysmorphism, microcephaly, and Hirschsprung disease. GOSHS is due to recessive mutations in KIAA1279, which encodes kinesin family member 1 binding protein (KIF1BP, also known as KBP). We examined the effects of inactivation of Kif1bp in mice. Mice lacking Kif1bp died shortly after birth, and exhibited smaller brains, olfactory bulbs and anterior commissures, and defects in the vagal and sympathetic innervation of the gut. Kif1bp was found to interact with Ret to regulate the development of the vagal innervation of the stomach. Although newborn Kif1bp -/- mice had neurons along the entire bowel, the colonization of the gut by neural crest-derived cells was delayed. The data show an essential in vivo role for KIF1BP in axon extension from some neurons, and the reduced size of the olfactory bulb also suggests additional roles for KIF1BP. Our mouse model provides a valuable resource to understand GOSHS.
- Published
- 2017
3. Ion Channel Expression in the Developing Enteric Nervous System
- Author
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Schubert, M, Hirst, CS, Foong, JPP, Stamp, LA, Fegan, E, Dent, S, Cooper, EC, Lomax, AE, Anderson, CR, Bornstein, JC, Young, HM, McKeown, SJ, Schubert, M, Hirst, CS, Foong, JPP, Stamp, LA, Fegan, E, Dent, S, Cooper, EC, Lomax, AE, Anderson, CR, Bornstein, JC, Young, HM, and McKeown, SJ
- Abstract
The enteric nervous system arises from neural crest-derived cells (ENCCs) that migrate caudally along the embryonic gut. The expression of ion channels by ENCCs in embryonic mice was investigated using a PCR-based array, RT-PCR and immunohistochemistry. Many ion channels, including chloride, calcium, potassium and sodium channels were already expressed by ENCCs at E11.5. There was an increase in the expression of numerous ion channel genes between E11.5 and E14.5, which coincides with ENCC migration and the first extension of neurites by enteric neurons. Previous studies have shown that a variety of ion channels regulates neurite extension and migration of many cell types. Pharmacological inhibition of a range of chloride or calcium channels had no effect on ENCC migration in cultured explants or neuritogenesis in vitro. The non-selective potassium channel inhibitors, TEA and 4-AP, retarded ENCC migration and neuritogenesis, but only at concentrations that also resulted in cell death. In summary, a large range of ion channels is expressed while ENCCs are colonizing the gut, but we found no evidence that ENCC migration or neuritogenesis requires chloride, calcium or potassium channel activity. Many of the ion channels are likely to be involved in the development of electrical excitability of enteric neurons.
- Published
- 2015
4. Chronic maxillary sinusitis in palaeopathology: A review of methods.
- Author
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Lee MJ, Siek TJ, and Hirst CS
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- Humans, Tomography, X-Ray Computed, Chronic Disease, Prevalence, Maxillary Sinusitis diagnosis, Sinusitis diagnosis
- Abstract
Objective: This study reviews the palaeopathological literature discussing maxillary sinusitis to examine current trends and issues within the study of this condition, and to make recommendations for future research in this area., Materials: Seventy-five studies were identified through a literature search of digital and physical sources., Methods: Information regarding study metadata, the populations investigated, sinusitis diagnostic criteria, and sinusitis prevalence was examined., Results: Populations from the UK and Europe were the most studied, reflecting both palaeopathology's systemic colonialism and academic legacies. Most studies used diagnostic criteria published in the mid-1990s, with some subsequent studies modifying these criteria., Conclusions: The diagnostic criteria from 1995 are widely used but do not include all possible bone changes seen within sinusitis. There is also a need for researchers to engage in issues of data reductionism when using descriptive categories for archaeological sites and populations., Significance: This paper provides considerations as to how the 1995 diagnostic criteria may be revised by future researchers and synthesises much of the published sinusitis prevalence data to assist researchers interested in the palaeopathology of respiratory disease., Limitations: More general osteological research, which includes palaeopathological information, was likely missed from this review due to the choice of key terms and languages used in the literature search., Suggestions for Further Research: Additional research into sinusitis in archaeological populations outside of Western Europe is required. Further work examining the ability to compare pathological data from macroscopic observation and medical imaging would be advantageous to palaeopathology as a whole., Competing Interests: Declaration of Competing Interest The authors declare no competing interests or sources of funding in the production of this work., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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5. Post-Closure Technique to Reduce Vascular Complications Related to Impella CP.
- Author
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Hirst CS, Thayer KL, Harwani N, and Kapur NK
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- Aged, Female, Hemorrhage etiology, Hemorrhage prevention & control, Humans, Male, Middle Aged, Retrospective Studies, Shock, Cardiogenic diagnosis, Shock, Cardiogenic etiology, Shock, Cardiogenic prevention & control, Treatment Outcome, Heart-Assist Devices adverse effects, Percutaneous Coronary Intervention adverse effects
- Abstract
Background: Use of percutaneous mechanical circulatory support has grown exponentially. Vascular complications remain a growing concern and best practices for device removal do not exist. We describe a novel post-closure technique for the next generation Impella CP removal and immediate hemostasis., Methods: This study is a single center, retrospective, exploratory analysis of 11 consecutive patients receiving an Impella CP for either high-risk PCI or cardiogenic shock and then referred for post-closure compared to 20 patients receiving manual compression for Impella CP removal between 2017 and 2019., Results: Mean age range was 62.7-65.4 years and 50-65% male between groups. Average duration of Impella CP treatment ranged from 3.4 to 5.2 days. Patients referred for post-closure had significantly lower rates of all-cause adverse vascular events (0% versus 40%; n = 0/11 versus n = 8/20; p = 0.01). There was no significant difference in BARC 3 or greater bleeding, transfusion requirement, hospitalization duration or intensive care duration between removal strategies., Conclusion: The novel post-closure technique may significantly reduce vascular complications associated with device removal and may improve clinical outcomes for these critically ill patients., Competing Interests: Declaration of competing interest CSH, KLT report no conflicts of interest. NKK is currently funded by the National Institutes of Health (RO1HL139785, RO1H133215) and has received research funding from Abiomed Inc., Abbott Inc., Boston Scientific Inc., MD Start Inc. and Maquet Cardiovascular Inc., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2022
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6. Successful Rescue Intervention of Internal Mammary Artery Anastomotic Site Acute Graft Failure With Direct New Generation Covered Stenting.
- Author
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Tahir H, Livesay J, Baljepally R, and Hirst CS
- Abstract
Acute, perioperative myocardial infarction (MI) from acute left internal mammary artery (LIMA) to left anterior descending (LAD) graft failure immediately following coronary artery bypass grafting (CABG) surgery is associated with significantly increased in-hospital mortality. The leading etiology of such acute graft failure is acute thrombosis, dissection, spasm, anastomosis failure or no-reflow phenomenon. Repeat bypass surgery carries incremental risk and may not be feasible in hemodynamically unstable patients. Traditional percutaneous coronary intervention (PCI), with or without stent placement is sometimes used in such cases; however, graft anatomy and lesion location increase procedural complexity and challenge technical feasibility. This is particularly true of the LIMA to LAD graft anastomosis, where PCI carries the risk of anastomotic site perforation or avulsion. Therefore, the best revascularization strategy for such a lesion involving the LIMA to LAD graft anastomosis in the immediate perioperative period remains unknown. We present a case of 75-year-old male who suffered an acute MI complicated by cardiogenic shock less than 24 h after two-vessel CABG. Selective angiography revealed acute LIMA to LAD anastomotic site closure, posing a risk for perforation if treated with traditional angioplasty or stenting. We successfully performed rescue PCI, by directly deploying a PK Papyrus covered stent (Biotronik, Berlin, Germany) across the anastomosis. Our case report describes the upfront (rather than a bail out) use of the new covered stent as a novel revascularization strategy to treat "perforation prone" LIMA to LAD anastomotic site acute graft failure., Competing Interests: The authors report no conflict of interest., (Copyright 2021, Tahir et al.)
- Published
- 2021
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7. Single stick access using a VA-ECMO arterial return cannula for coronary intervention in cardiogenic shock.
- Author
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Kapur NK, Hirst CS, Davila CD, and Garcia R
- Subjects
- Aged, Cannula, Humans, Male, Treatment Outcome, Extracorporeal Membrane Oxygenation, Percutaneous Coronary Intervention adverse effects, Shock, Cardiogenic diagnosis, Shock, Cardiogenic etiology, Shock, Cardiogenic therapy
- Abstract
Use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is growing exponentially for cardiogenic shock and cardiac arrest, and many of these patients require percutaneous coronary intervention (PCI). In some cases, radial arterial access may not feasible among patients with peripheral vascular disease or if larger diameter guide catheters are required. Further, VA-ECMO is commonly used in combination with an intra-aortic balloon pump or Impella, thereby limiting vascular access options and increasing the risk of vascular complications including bleeding and limb ischemia. For these reasons, new approaches to perform PCI without the need for an additional arterial puncture are required. We describe a case of a 70-year-old man with cardiogenic shock referred for high-risk PCI while supported with VA-ECMO and an Impella CP and illustrate a novel method for single-stick access for PCI through the return cannula of the VA-ECMO circuit., (© 2020 Wiley Periodicals LLC.)
- Published
- 2021
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8. Right Atrial Pressure Is Associated With Outcomes in Patient With Cardiogenic Shock Receiving Acute Mechanical Circulatory Support.
- Author
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Davila CD, Esposito M, Hirst CS, Morine K, Jorde L, Newman S, Paruchuri V, Whitehead E, Thayer KL, and Kapur NK
- Abstract
Background: We describe the association between longitudinal hemodynamic changes and clinical outcomes in patients with cardiogenic shock (CS) receiving acute mechanical circulatory support devices (AMCS) at a single center. We hypothesized that improved right atrial pressure is associated with better survival in CS. Methods: Retrospective analysis of patients from Tufts Medical Center that received AMCS for CS. Baseline characteristics and invasive hemodynamics were collected, analyzed, and correlated against outcomes. Hemodynamics were recorded at different time intervals during index admission [pre-AMCS, 24 h after AMCS (post AMCS), and last available set of hemodynamics (final-AMCS)]. Logistic regression was performed to determine variables associated with in-hospital mortality. Results: A total of 76 patients had longitudinal hemodynamics available. In hospital mortality occurred in 46% of the cohort. Mean baseline right atrial pressure (RAP) was significantly higher among non-survivors vs. survivors (19.5+6.6 vs. 16.4+5.3 mmHg). Change in right atrial pressure from baseline to before device removal (ΔRA:final AMCS-pre AMCS) was significantly different between survivors and non survivors (-6.5 ± 6.9 mmHg vs. -2.5 ± 6.2 mmHg p = 0.03). Unadjusted logistic regression revealed baseline RAP (OR: 1.1 95% CI: 1.0-1.2), 24 h post device implant RAP (OR: 1.3 95% CI: 1.1-1.4), and final RAP (OR: 1.3 95% CI: 1.1-1.5) to be significant predictors of in-hospital mortality. In a multivariate logistic regression baseline RAP was no longer significantly associated with mortality in the overall cohort, while 24 h (OR: 1.26 95% CI: 1.1-1.5) and final RAP (OR: 1.3 95% CI: 1.1-1.6) remained statistically significant. Conclusion: We report a novel retrospective analysis of hemodynamic changes in patients with CS receiving AMCS. Our findings identify the potential importance of venous congestion as a prognostic marker of mortality. Furthermore, early decongestion or reduced RA pressure is associated with better survival in these critically ill CS patients. These observations suggest the need for further study in larger retrospective and prospective cohorts of patients with varying degrees of CS severity., Competing Interests: NK has received research funding from Abbott; Abiomed Inc., Boston Scientific Inc.,Getinge; LivaNova; MD Start Inc., and preCARDIA Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Davila, Esposito, Hirst, Morine, Jorde, Newman, Paruchuri, Whitehead, Thayer and Kapur.)
- Published
- 2021
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9. Transaxillary Intra-Aortic Balloon Pump Deployment Through a Novel Braided Sheath for Advanced Heart Failure Patients Requiring an Extended Duration of Temporary Circulatory Support.
- Author
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Hirst CS, Davila CD, Garcia R, and Kapur NK
- Subjects
- Axillary Artery, Heart Failure, Humans, Intra-Aortic Balloon Pumping, Retrospective Studies, Heart-Assist Devices
- Abstract
For decompensated advanced heart failure patients, the intra-aortic balloon pump (IABP) is a commonly used mechanical circulatory support (MCS) device used to support pharmacotherapy-refractory myopaths. In the United States, the heart allocation policy was revised in 2018, placing patients who may receive a clinically indicated temporary MCS device, like an IABP, at elevated medical urgency on the transplantation waiting list. Percutaneous transaxillary IABP delivery for the decompensated advanced heart failure patient is a safe, tolerable and efficacious alternative to traditional transfemoral deployment, and allows for ambulation and meaningful physical therapy engagement in the patient who may require an extended duration of support awaiting advanced therapies. We present two cases of percutaneous transaxillary IABP delivery via the Super Arrow-Flex braided sheath (Teleflex, Morrisville, NC) in advanced heart failure patients. The Super Arrow-Flex Sheath is a braided, durable, non-kinking conduit that can negotiate tortuous vascularity while maintaining its internal integrity; transaxillary IABP delivery through this sheath offers the patient a wide latitude of ipsilateral upper extremity movement and ambulation with minimal risk of damage to the IABP catheter. The Super Arrow-Flex sheath may improve transaxillary IABP security, durability and longevity in the advanced heart failure population for whom long-term IABP is anticipated., (Copyright © 2020. Published by Elsevier Inc.)
- Published
- 2020
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10. Genetic Alterations in the PI3K/AKT Pathway and Baseline AKT Activity Define AKT Inhibitor Sensitivity in Breast Cancer Patient-derived Xenografts.
- Author
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Gris-Oliver A, Palafox M, Monserrat L, Brasó-Maristany F, Òdena A, Sánchez-Guixé M, Ibrahim YH, Villacampa G, Grueso J, Parés M, Guzmán M, Rodríguez O, Bruna A, Hirst CS, Barnicle A, de Bruin EC, Reddy A, Schiavon G, Arribas J, Mills GB, Caldas C, Dienstmann R, Prat A, Nuciforo P, Razavi P, Scaltriti M, Turner NC, Saura C, Davies BR, Oliveira M, and Serra V
- Subjects
- Animals, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast pathology, Breast surgery, Breast Neoplasms genetics, Breast Neoplasms pathology, Chemotherapy, Adjuvant methods, Class I Phosphatidylinositol 3-Kinases genetics, DNA Mutational Analysis, Female, Humans, Mastectomy, Mice, Mutation, Paclitaxel pharmacology, Paclitaxel therapeutic use, Prognosis, Protein Kinase Inhibitors therapeutic use, Proto-Oncogene Proteins c-akt genetics, Pyrimidines pharmacology, Pyrimidines therapeutic use, Pyrroles pharmacology, Pyrroles therapeutic use, Ribosomal Protein S6 Kinases, 70-kDa metabolism, Signal Transduction drug effects, TOR Serine-Threonine Kinases genetics, Tuberous Sclerosis Complex 1 Protein genetics, Xenograft Model Antitumor Assays, Antineoplastic Combined Chemotherapy Protocols pharmacology, Biomarkers, Tumor genetics, Breast Neoplasms therapy, Drug Resistance, Neoplasm genetics, Protein Kinase Inhibitors pharmacology
- Abstract
Purpose: AZD5363/capivasertib is a pan-AKT catalytic inhibitor with promising activity in combination with paclitaxel in triple-negative metastatic breast cancer harboring PI3K/AKT-pathway alterations and in estrogen receptor-positive breast cancer in combination with fulvestrant. Here, we aimed to identify response biomarkers and uncover mechanisms of resistance to AZD5363 and its combination with paclitaxel., Experimental Design: Genetic and proteomic markers were analyzed in 28 HER2-negative patient-derived xenografts (PDXs) and in patient samples, and correlated to AZD5363 sensitivity as single agent and in combination with paclitaxel., Results: Four PDX were derived from patients receiving AZD5363 in the clinic which exhibited concordant treatment response. Mutations in PIK3CA / AKT1 and absence of mTOR complex 1 (mTORC1)-activating alterations, for example, in MTOR or TSC1 , were associated with sensitivity to AZD5363 monotherapy. Interestingly, excluding PTEN from the composite biomarker increased its accuracy from 64% to 89%. Moreover, resistant PDXs exhibited low baseline pAKT S473 and residual pS6 S235 upon treatment, suggesting that parallel pathways bypass AKT/S6K1 signaling in these models. We identified two mechanisms of acquired resistance to AZD5363: cyclin D1 overexpression and loss of AKT1 p.E17K., Conclusions: This study provides insight into putative predictive biomarkers of response and acquired resistance to AZD5363 in HER2-negative metastatic breast cancer., (©2020 American Association for Cancer Research.)
- Published
- 2020
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11. Honeycomb sterna: an unusual case of a developmental abnormality in the sternum.
- Author
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Hirst CS, White S, Siek T, and Gasparik A
- Subjects
- Adult, Bone Diseases, Developmental classification, Bone Diseases, Developmental embryology, Humans, Osteogenesis, Sternum embryology, Bone Diseases, Developmental diagnosis, Sternum abnormalities
- Abstract
This report details an unusual case of a human sternal developmental abnormality of an anatomical specimen part of the skeletal collection curated by University College London, Anthropology Department skeletal collection. This rarely reported developmental abnormality is caused by the non-fusion of lateral ossification centres in the sternebrae, resulting in the mesosternum having a honeycomb-like appearance. Sternal defects are typically underreported in the clinical literature as many cases being asymptomatic that they are typically diagnosed incidentally, as such there is a dearth in our current understanding of the development and anatomical variants of the sternum. Although in recent years, large-scale CT studies have investigated the prevalence of sternal developmental abnormalities, these studies have not reported sternal defects similar to the individual presented in this report. While most sternal defects are clinically uneventful, the lack of awareness of these variants can result in misinterpretation of radiological and pathological findings as such an understanding of anatomical variants even when asymptomatic is vital.
- Published
- 2020
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12. A phase II study to assess the safety and efficacy of the dual mTORC1/2 inhibitor vistusertib in relapsed, refractory DLBCL.
- Author
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Eyre TA, Hildyard C, Hamblin A, Ali AS, Houlton A, Hopkins L, Royston D, Linton KM, Pettitt A, Rule S, Cwynarski K, Barrington SF, Warbey V, Wrench D, Barrans S, Hirst CS, Panchal A, Roudier MP, Harrington EA, Davies A, and Collins GP
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, B-Lymphocyte Subsets pathology, Benzamides therapeutic use, Drug Resistance, Neoplasm, Female, Gastrointestinal Diseases chemically induced, Humans, Kaplan-Meier Estimate, Lymphoma, Large B-Cell, Diffuse pathology, Male, Middle Aged, Morpholines therapeutic use, Neoplastic Stem Cells pathology, Progression-Free Survival, Protein Kinase Inhibitors therapeutic use, Pyrimidines therapeutic use, Rituximab administration & dosage, Rituximab adverse effects, Antineoplastic Agents adverse effects, Benzamides adverse effects, Lymphoma, Large B-Cell, Diffuse drug therapy, Mechanistic Target of Rapamycin Complex 1 antagonists & inhibitors, Mechanistic Target of Rapamycin Complex 2 antagonists & inhibitors, Molecular Targeted Therapy, Morpholines adverse effects, Neoplasm Proteins antagonists & inhibitors, Protein Kinase Inhibitors adverse effects, Pyrimidines adverse effects, Salvage Therapy
- Abstract
Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are unfit for or relapsed postautologous stem-cell transplantation have poor outcomes. Historically, mTORC1 inhibitors have produced responses in approximately 30% of patients in this setting. mTORC1 inhibitor efficacy may be limited by resistance mechanisms including AKT activation by mTORC2. To date, dual mTORC1/2 inhibitors targeting both the TORC1 and TORC2 complexes have not been investigated in DLBCL. This phase II trial investigated the oral dual mTORC1/2 inhibitor vistusertib in an intermittent dosing schedule of 125 mg b.d. for 2 days per week. Thirty patients received vistusertib and six received vistusertib-rituximab for up to six cycles (28-day cycles). Two partial responses were achieved on monotherapy. Durations of response were 57 and 62 days, respectively, for these patients. 19% had stable disease within six cycles. In the monotherapy arm, the median progression-free survival was1.69 (95% confidence interval [CI] 1.61-2.14) months and median overall survival was 6.58 (95% CI 3.81-not reached) months, respectively. The median duration of response or stable disease across the trial duration was 153 days (95% CI 112-not reached). Tumour responses according to positron emission tomography/computed tomography versus computed tomography were concordant. There were no differences noted in tumour volume response according to cell of origin by either gene expression profiling or immunohistochemistry. Vistusertib ± rituximab was well tolerated; across 36 patients 86% of adverse events were grade (G) 1-2. Common vistusertib-related adverse events were similar to those described with mTORC1 inhibitors: nausea (47% G1-2), diarrhoea (27% G1-2, 6% G3), fatigue (30% G1-2, 3% G3), mucositis (25% G1-2, 6% G3), vomiting (17% G1-2), and dyspepsia (14% G1-2). Dual mTORC1/2 inhibitors do not clearly confer an advantage over mTORC1 inhibitors in relapsed or refractory DLBCL. Potential resistance mechanisms are discussed within., (© 2019 John Wiley & Sons, Ltd.)
- Published
- 2019
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13. Spinal neural tube closure depends on regulation of surface ectoderm identity and biomechanics by Grhl2.
- Author
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Nikolopoulou E, Hirst CS, Galea G, Venturini C, Moulding D, Marshall AR, Rolo A, De Castro SCP, Copp AJ, and Greene NDE
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- Actomyosin genetics, Actomyosin metabolism, Animals, Biomechanical Phenomena, Cadherins metabolism, Ectoderm cytology, Ectoderm embryology, Ectoderm metabolism, Epithelial Cells metabolism, Intercellular Junctions genetics, Intercellular Junctions metabolism, Mice, Neural Tube metabolism, SOXB1 Transcription Factors metabolism, Stress, Mechanical, Transcription Factors metabolism, Embryo, Mammalian metabolism, Gene Expression Regulation, Developmental, Neural Tube embryology, Neuroepithelial Cells metabolism, Neurulation genetics, Transcription Factors genetics
- Abstract
Lack or excess expression of the surface ectoderm-expressed transcription factor Grainyhead-like2 (Grhl2), each prevent spinal neural tube closure. Here we investigate the causative mechanisms and find reciprocal dysregulation of epithelial genes, cell junction components and actomyosin properties in Grhl2 null and over-expressing embryos. Grhl2 null surface ectoderm shows a shift from epithelial to neuroepithelial identity (with ectopic expression of N-cadherin and Sox2), actomyosin disorganisation, cell shape changes and diminished resistance to neural fold recoil upon ablation of the closure point. In contrast, excessive abundance of Grhl2 generates a super-epithelial surface ectoderm, in which up-regulation of cell-cell junction proteins is associated with an actomyosin-dependent increase in local mechanical stress. This is compatible with apposition of the neural folds but not with progression of closure, unless myosin activity is inhibited. Overall, our findings suggest that Grhl2 plays a crucial role in regulating biomechanical properties of the surface ectoderm that are essential for spinal neurulation.
- Published
- 2019
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14. Hypertrophic osteoarthropathy in an adult macaque.
- Author
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Hirst CS and Waldron T
- Subjects
- Animals, Bone and Bones diagnostic imaging, Bone and Bones pathology, Diagnosis, Differential, History, Ancient, London, Monkey Diseases diagnostic imaging, Monkey Diseases pathology, Osteoarthropathy, Primary Hypertrophic diagnostic imaging, Osteoarthropathy, Primary Hypertrophic pathology, Osteoarthropathy, Primary Hypertrophic veterinary, Paleopathology, Macaca, Monkey Diseases history, Osteoarthropathy, Primary Hypertrophic history
- Abstract
Objective: To evaluate through differential diagnosis whether hypertrophic osteoarthropathy was present on an adult macaque skeleton., Materials: Skeletal remains of a well-preserved adult macaque (Macaca) of unknown species curated by the archaeology department at University College London., Methods: Macroscopic and radiographic evaluation of pathological lesions., Results: Widespread bilateral and symmetrical periosteal new bone growth primarily affecting the limbs was observed., Conclusion: A careful differential diagnosis of the lesions and comparison with previously published cases of hypertrophic osteoarthropathy among humans and non-humans suggests this animal displays a case of Hypertrophic osteoarthropathy., Significance: Only been three reported cases of HOA in non-human primates have been reported, and all were apes. This study serves as the first reported case of HOA among non-hominoid simians, providing a detailed description of the skeletal lesions to aid future with paleopathological analyses., Limitations: Small sample sizes for comparison and lack of context for this specimen limits discussion of the scope of this disease among non-human primates., Suggestions for Further Research: Re-evaluate skeletal collections which have not been subject to recent osteological and pathological analysis., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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15. Deployment of acute mechanical circulatory support devices via the axillary artery.
- Author
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Tayal R, Hirst CS, Garg A, and Kapur NK
- Subjects
- Axillary Artery, Extracorporeal Membrane Oxygenation methods, Heart Ventricles physiopathology, Humans, Intra-Aortic Balloon Pumping methods, Shock, Cardiogenic physiopathology, Heart Failure therapy, Heart-Assist Devices, Shock, Cardiogenic therapy
- Abstract
Introduction : Use of acute mechanical circulatory support (MCS) devices for high-risk cardiac intervention, cardiogenic shock, and advanced heart failure is growing. Alternate vascular access options for these devices remains a clinical challenge. Building on experience from trans-aortic valve replacement procedures, the axillary artery is becoming a common access route for acute MCS and represents an important advance in the development of acute MCS technologies. Areas covered : Authors review the clinical data and technical aspect of acute MCS deployment via the axillary artery. Axillary access is particularly useful for patients: 1) with severe peripheral vascular disease, 2) with hostile femoral access due to infection, indwelling endovascular devices, or obesity, and 3) to provide early mobility and ambulation. In this review, we discuss the deployment, technical issues and hemostasis regarding the use of intraaortic balloon pump, specifically, axillary intraaortic balloon pumps, trans-valvular left ventricular Impella pumps and arterial outflow of VA-ECMO. Expert opinion : Vascular comorbidities or device design may limit the traditional iliofemoral access route for acute mechanical circulatory support devices. Large bore access for the deployment of these devices through the axillary artery is feasible and safe when appropriate vascular access and closure techniques are used.
- Published
- 2019
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16. Counterpulsation requires pulsation: IABP use in patients with heart failure without acute MI.
- Author
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Kapur NK and Hirst CS
- Subjects
- Hemodynamics, Humans, Intra-Aortic Balloon Pumping, Shock, Cardiogenic, Counterpulsation, Heart Failure, Myocardial Infarction
- Abstract
Limited data exploring the utility of IABPs in shock without acute myocardial infarction exist. Counterpulsation pumps depend on native LV contractile function. Hemodynamic monitoring with a pulmonary artery catheter should help guide management of the cardiogenic shock patient. More studies are required to identify the optimal patient population and hemodynamic parameters best suited for IABP therapy., (© 2018 Wiley Periodicals, Inc.)
- Published
- 2018
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17. Publisher Correction: Kif1bp loss in mice leads to defects in the peripheral and central nervous system and perinatal death.
- Author
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Hirst CS, Stamp LA, Bergner AJ, Hao MM, Tran MX, Morgan JM, Dutschmann M, Allen AM, Paxinos G, Furlong TM, McKeown SJ, and Young HM
- Abstract
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
- Published
- 2018
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18. Neural tube closure depends on expression of Grainyhead-like 3 in multiple tissues.
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De Castro SCP, Hirst CS, Savery D, Rolo A, Lickert H, Andersen B, Copp AJ, and Greene NDE
- Subjects
- Animals, DNA-Binding Proteins deficiency, DNA-Binding Proteins genetics, Embryonic Development, Gene Expression Regulation, Developmental, Genes, Reporter, Germ Layers metabolism, Mice, Mice, Knockout, Mice, Transgenic, Neural Plate metabolism, Neural Tube Defects embryology, Neural Tube Defects pathology, Organ Specificity, RNA, Messenger biosynthesis, Spinal Dysraphism embryology, Spinal Dysraphism genetics, Transcription Factors deficiency, Transcription Factors genetics, DNA-Binding Proteins physiology, Neural Tube physiology, Neural Tube Defects genetics, Neurulation genetics, Transcription Factors physiology
- Abstract
Failure of neural tube closure leads to neural tube defects (NTDs), common congenital abnormalities in humans. Among the genes whose loss of function causes NTDs in mice, Grainyhead-like3 (Grhl3) is essential for spinal neural tube closure, with null mutants exhibiting fully penetrant spina bifida. During spinal neurulation Grhl3 is initially expressed in the surface (non-neural) ectoderm, subsequently in the neuroepithelial component of the neural folds and at the node-streak border, and finally in the hindgut endoderm. Here, we show that endoderm-specific knockout of Grhl3 causes late-arising spinal NTDs, preceded by increased ventral curvature of the caudal region which was shown previously to suppress closure of the spinal neural folds. This finding supports the hypothesis that diminished Grhl3 expression in the hindgut is the cause of spinal NTDs in the curly tail, carrying a hypomorphic Grhl3 allele. Complete loss of Grhl3 function produces a more severe phenotype in which closure fails earlier in neurulation, before the stage of onset of expression in the hindgut of wild-type embryos. This implicates additional tissues and NTD mechanisms in Grhl3 null embryos. Conditional knockout of Grhl3 in the neural plate and node-streak border has minimal effect on closure, suggesting that abnormal function of surface ectoderm, where Grhl3 transcripts are first detected, is primarily responsible for early failure of spinal neurulation in Grhl3 null embryos., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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19. Kif1bp loss in mice leads to defects in the peripheral and central nervous system and perinatal death.
- Author
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Hirst CS, Stamp LA, Bergner AJ, Hao MM, Tran MX, Morgan JM, Dutschmann M, Allen AM, Paxinos G, Furlong TM, McKeown SJ, and Young HM
- Abstract
Goldberg-Shprintzen syndrome is a poorly understood condition characterized by learning difficulties, facial dysmorphism, microcephaly, and Hirschsprung disease. GOSHS is due to recessive mutations in KIAA1279, which encodes kinesin family member 1 binding protein (KIF1BP, also known as KBP). We examined the effects of inactivation of Kif1bp in mice. Mice lacking Kif1bp died shortly after birth, and exhibited smaller brains, olfactory bulbs and anterior commissures, and defects in the vagal and sympathetic innervation of the gut. Kif1bp was found to interact with Ret to regulate the development of the vagal innervation of the stomach. Although newborn Kif1bp
-/- mice had neurons along the entire bowel, the colonization of the gut by neural crest-derived cells was delayed. The data show an essential in vivo role for KIF1BP in axon extension from some neurons, and the reduced size of the olfactory bulb also suggests additional roles for KIF1BP. Our mouse model provides a valuable resource to understand GOSHS.- Published
- 2017
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20. Spontaneous calcium waves in the developing enteric nervous system.
- Author
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Hao MM, Bergner AJ, Hirst CS, Stamp LA, Casagranda F, Bornstein JC, Boesmans W, Vanden Berghe P, and Young HM
- Subjects
- Animals, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neural Crest cytology, Neurogenesis physiology, Organ Culture Techniques, Purinergic P2X Receptor Antagonists pharmacology, Purinergic P2Y Receptor Antagonists pharmacology, Calcium Signaling physiology, Enteric Nervous System embryology, Neural Crest embryology, Receptors, Purinergic P2X metabolism, Receptors, Purinergic P2Y metabolism
- Abstract
The enteric nervous system (ENS) is an extensive network of neurons in the gut wall that arises from neural crest-derived cells. Like other populations of neural crest cells, it is known that enteric neural crest-derived cells (ENCCs) influence the behaviour of each other and therefore must communicate. However, little is known about how ENCCs communicate with each other. In this study, we used Ca
2+ imaging to examine communication between ENCCs in the embryonic gut, using mice where ENCCs express a genetically-encoded calcium indicator. Spontaneous propagating calcium waves were observed between neighbouring ENCCs, through both neuronal and non-neuronal ENCCs. Pharmacological experiments showed wave propagation was not mediated by gap junctions, but by purinergic signalling via P2 receptors. The expression of several P2X and P2Y receptors was confirmed using RT-PCR. Furthermore, inhibition of P2 receptors altered the morphology of the ENCC network, without affecting neuronal differentiation or ENCC proliferation. It is well established that purines participate in synaptic transmission in the mature ENS. Our results describe, for the first time, purinergic signalling between ENCCs during pre-natal development, which plays roles in the propagation of Ca2+ waves between ENCCs and in ENCC network formation. One previous study has shown that calcium signalling plays a role in sympathetic ganglia formation; our results suggest that calcium waves are likely to be important for enteric ganglia development., (Copyright © 2017 Elsevier Inc. All rights reserved.)- Published
- 2017
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- View/download PDF
21. Arrhythmias in a long-term adult survivor with uncorrected tetralogy of Fallot: Case report and review of the literature.
- Author
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Hirst CS, Jureidini S, and Hauptman PJ
- Subjects
- Comorbidity, Humans, Male, Middle Aged, Risk Factors, Survival Rate, Arrhythmias, Cardiac diagnosis, Arrhythmias, Cardiac mortality, Survivors statistics & numerical data, Tetralogy of Fallot diagnosis, Tetralogy of Fallot mortality
- Abstract
We present a case of a middle-aged adult with uncorrected Tetralogy of Fallot (TOF) with pulmonary atresia who developed symptomatic supraventricular and ventricular arrhythmias. The lack of data regarding management of electrical and other complications in adults with uncorrected TOF is highlighted and emphasizes the need for a registry to better understand the medical management of long-standing adult survivors., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
22. Changes in Nicotinic Neurotransmission during Enteric Nervous System Development.
- Author
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Foong JP, Hirst CS, Hao MM, McKeown SJ, Boesmans W, Young HM, Bornstein JC, and Vanden Berghe P
- Subjects
- Animals, Animals, Newborn, Enteric Nervous System drug effects, Female, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nicotinic Antagonists pharmacology, Pregnancy, Synaptic Transmission drug effects, Enteric Nervous System embryology, Enteric Nervous System growth & development, Receptors, Nicotinic physiology, Synaptic Transmission physiology
- Abstract
Acetylcholine-activating pentameric nicotinic receptors (nAChRs) are an essential mode of neurotransmission in the enteric nervous system (ENS). In this study, we examined the functional development of specific nAChR subtypes in myenteric neurons using Wnt1-Cre;R26R-GCaMP3 mice, where all enteric neurons and glia express the genetically encoded calcium indicator, GCaMP3. Transcripts encoding α3, α4, α7, β2, and β4 nAChR subunits were already expressed at low levels in the E11.5 gut and by E14.5 and, thereafter, α3 and β4 transcripts were the most abundant. The effect of specific nAChR subtype antagonists on evoked calcium activity in enteric neurons was investigated at different ages. Blockade of the α3β4 receptors reduced electrically and chemically evoked calcium responses at E12.5, E14.5, and P0. In addition to the α3β4 antagonist, antagonists to α3β2 and α4β2 also significantly reduced responses by P10-11 and in adult preparations. Therefore, there is an increase in the diversity of functional nAChRs during postnatal development. However, an α7 nAChR antagonist had no effect at any age. Furthermore, at E12.5 we found evidence for unconventional receptors that were responsive to the nAChR agonists 1-dimethyl-4-phenylpiperazinium and nicotine, but were insensitive to the general nicotinic blocker, hexamethonium. Migration, differentiation, and neuritogenesis assays did not reveal a role for nAChRs in these processes during embryonic development. In conclusion, there are significant changes in the contribution of different nAChR subunits to synaptic transmission during ENS development, even after birth. This is the first study to investigate the development of cholinergic transmission in the ENS., (Copyright © 2015 the authors 0270-6474/15/357106-10$15.00/0.)
- Published
- 2015
- Full Text
- View/download PDF
23. Ion channel expression in the developing enteric nervous system.
- Author
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Hirst CS, Foong JP, Stamp LA, Fegan E, Dent S, Cooper EC, Lomax AE, Anderson CR, Bornstein JC, Young HM, and McKeown SJ
- Subjects
- 4-Aminopyridine pharmacology, Animals, Cell Movement drug effects, Down-Regulation, Embryo, Mammalian cytology, Enteric Nervous System cytology, Enteric Nervous System growth & development, Enteric Nervous System metabolism, Ion Channels antagonists & inhibitors, Mice, Mice, Inbred C57BL, Microscopy, Fluorescence, Neural Crest cytology, Neurites physiology, Neurogenesis drug effects, Tetraethylammonium pharmacology, Up-Regulation, Ion Channels metabolism, Neural Crest metabolism
- Abstract
The enteric nervous system arises from neural crest-derived cells (ENCCs) that migrate caudally along the embryonic gut. The expression of ion channels by ENCCs in embryonic mice was investigated using a PCR-based array, RT-PCR and immunohistochemistry. Many ion channels, including chloride, calcium, potassium and sodium channels were already expressed by ENCCs at E11.5. There was an increase in the expression of numerous ion channel genes between E11.5 and E14.5, which coincides with ENCC migration and the first extension of neurites by enteric neurons. Previous studies have shown that a variety of ion channels regulates neurite extension and migration of many cell types. Pharmacological inhibition of a range of chloride or calcium channels had no effect on ENCC migration in cultured explants or neuritogenesis in vitro. The non-selective potassium channel inhibitors, TEA and 4-AP, retarded ENCC migration and neuritogenesis, but only at concentrations that also resulted in cell death. In summary, a large range of ion channels is expressed while ENCCs are colonizing the gut, but we found no evidence that ENCC migration or neuritogenesis requires chloride, calcium or potassium channel activity. Many of the ion channels are likely to be involved in the development of electrical excitability of enteric neurons.
- Published
- 2015
- Full Text
- View/download PDF
24. Over-expression of Grhl2 causes spina bifida in the Axial defects mutant mouse.
- Author
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Brouns MR, De Castro SC, Terwindt-Rouwenhorst EA, Massa V, Hekking JW, Hirst CS, Savery D, Munts C, Partridge D, Lamers W, Köhler E, van Straaten HW, Copp AJ, and Greene ND
- Subjects
- Animals, Cell Proliferation, Chromosome Mapping, Chromosomes, Mammalian genetics, Female, Gene Silencing, Genetic Linkage, Humans, Hybridization, Genetic, Lower Gastrointestinal Tract abnormalities, Lower Gastrointestinal Tract cytology, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Mutant Strains, Mutation, Spinal Dysraphism embryology, Transcription Factors metabolism, Transcription, Genetic, Up-Regulation, Spinal Dysraphism genetics, Transcription Factors genetics
- Abstract
Cranial neural tube defects (NTDs) occur in mice carrying mutant alleles of many different genes, whereas isolated spinal NTDs (spina bifida) occur in fewer models, despite being common human birth defects. Spina bifida occurs at high frequency in the Axial defects (Axd) mouse mutant but the causative gene is not known. In the current study, the Axd mutation was mapped by linkage analysis. Within the critical genomic region, sequencing did not reveal a coding mutation whereas expression analysis demonstrated significant up-regulation of grainyhead-like 2 (Grhl2) in Axd mutant embryos. Expression of other candidate genes did not differ between genotypes. In order to test the hypothesis that over-expression of Grhl2 causes Axd NTDs, we performed a genetic cross to reduce Grhl2 function in Axd heterozygotes. Grhl2 loss of function mutant mice were generated and displayed both cranial and spinal NTDs. Compound heterozygotes carrying both loss (Grhl2 null) and putative gain of function (Axd) alleles exhibited normalization of spinal neural tube closure compared with Axd/+ littermates, which exhibit delayed closure. Grhl2 is expressed in the surface ectoderm and hindgut endoderm in the spinal region, overlapping with grainyhead-like 3 (Grhl3). Axd mutants display delayed eyelid closure, as reported in Grhl3 null embryos. Moreover, Axd mutant embryos exhibited increased ventral curvature of the spinal region and reduced proliferation in the hindgut, reminiscent of curly tail embryos, which carry a hypomorphic allele of Grhl3. Overall, our data suggest that defects in Axd mutant embryos result from over-expression of Grhl2.
- Published
- 2011
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- View/download PDF
25. SoxB1 transcription factors restrict organizer gene expression by repressing multiple events downstream of Wnt signalling.
- Author
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Shih YH, Kuo CL, Hirst CS, Dee CT, Liu YR, Laghari ZA, and Scotting PJ
- Subjects
- Active Transport, Cell Nucleus, Animals, Animals, Genetically Modified, Biomarkers metabolism, Homeodomain Proteins genetics, Homeodomain Proteins metabolism, Mesoderm metabolism, Nodal Signaling Ligands metabolism, Protein Binding, SOXB1 Transcription Factors genetics, Transcription, Genetic, Wnt Proteins metabolism, Zebrafish genetics, Zebrafish Proteins genetics, Zebrafish Proteins metabolism, beta Catenin genetics, beta Catenin metabolism, Gene Expression Regulation, Developmental, SOXB1 Transcription Factors metabolism, Signal Transduction, Zebrafish embryology, Zebrafish metabolism
- Abstract
Formation of the organizer is one of the most central patterning events in vertebrate development. Organizer-derived signals are responsible for establishing the CNS and patterning the dorsal ventral axis. The mechanisms promoting organizer formation are known to involve cooperation between Nodal and Wnt signalling. However, the organizer forms in a very restricted region, suggesting the presence of mechanisms that repress its formation. Here, we show in zebrafish that the transcription factor Sox3 represses multiple steps in the signalling events that lead to organizer formation. Although beta-catenin, Bozozok and Squint are known to play major roles in establishing the dorsal organizer in vertebrate embryos, overexpression of any of these is insufficient to induce robust expression of markers of the organizer in ectopic positions in the animal pole, where Sox3 is strongly expressed. We show that a dominant-negative nuclear localisation mutant of Sox3 can cause ectopic expression of organizer genes via a mechanism that activates all of these earlier factors, resulting in later axis duplication including major bifurcations of the CNS. We also find that the related SoxB1 factor, Sox19b, can act redundantly with Sox3 in these effects. It therefore seems that the broad expression of these SoxB1 genes throughout the early epiblast and their subsequent restriction to the ectoderm is a primary regulator of when and where the organizer forms.
- Published
- 2010
- Full Text
- View/download PDF
26. Sox3 regulates both neural fate and differentiation in the zebrafish ectoderm.
- Author
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Dee CT, Hirst CS, Shih YH, Tripathi VB, Patient RK, and Scotting PJ
- Subjects
- 5' Untranslated Regions genetics, Animals, Base Sequence, Biomarkers metabolism, Body Patterning, Central Nervous System embryology, DNA-Binding Proteins genetics, Ear abnormalities, Ear embryology, Ectoderm embryology, Embryo, Nonmammalian cytology, Fibroblast Growth Factors metabolism, Gene Expression Regulation, Developmental, High Mobility Group Proteins genetics, Molecular Sequence Data, Neural Plate cytology, Neurons metabolism, SOXB1 Transcription Factors, Signal Transduction, Skull abnormalities, Skull embryology, Transcription Factors genetics, Zebrafish genetics, Cell Differentiation, Cell Lineage, DNA-Binding Proteins metabolism, Ectoderm cytology, High Mobility Group Proteins metabolism, Neurons cytology, Transcription Factors metabolism, Zebrafish embryology
- Abstract
Little is known of the first transcriptional events that regulate neural fate in response to extracellular signals such as Bmps and Fgfs. Sox3 is one of the earliest transcription factors to be expressed in the developing CNS and has been shown to be regulated by these signalling pathways. We have used both gain- and loss-of-function experiments in zebrafish to elucidate the role of Sox3 in determining neural fate. Ectopic Sox3 caused induction of neural tissue from a very early stage of cell specification in the ectoderm and this effect was maintained such that large domains of additional CNS were apparent, including almost complete duplications of the CNS. Knock-down of Sox3 using morpholinos resulted in a reduction in the size of the CNS, ears and eyes and subsequent inhibition of some aspects of neurogenesis. Our data also suggest that the pro-neural effects of Sox3 can compensate for inhibition of Fgf signalling in inducing neural tissue but it is not sufficient to maintain neural fate, suggesting the presence of Sox3-independent roles of Fgf at later stages.
- Published
- 2008
- Full Text
- View/download PDF
27. Epibranchial and otic placodes are induced by a common Fgf signal, but their subsequent development is independent.
- Author
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Sun SK, Dee CT, Tripathi VB, Rengifo A, Hirst CS, and Scotting PJ
- Subjects
- Animals, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Ectoderm cytology, Ectoderm metabolism, Fibroblast Growth Factor 3 genetics, Fibroblast Growth Factor 3 metabolism, Fibroblast Growth Factors genetics, Forkhead Transcription Factors genetics, Forkhead Transcription Factors metabolism, Gene Expression Regulation, Developmental, High Mobility Group Proteins genetics, High Mobility Group Proteins metabolism, In Situ Hybridization, Models, Biological, Mutation, Neurons, Afferent cytology, Neurons, Afferent metabolism, SOXB1 Transcription Factors, Signal Transduction, Transcription Factors genetics, Transcription Factors metabolism, Zebrafish genetics, Zebrafish Proteins genetics, Fibroblast Growth Factors metabolism, Peripheral Nerves embryology, Peripheral Nerves metabolism, Zebrafish embryology, Zebrafish metabolism, Zebrafish Proteins metabolism
- Abstract
The epibranchial placodes are cranial, ectodermal thickenings that give rise to sensory neurons of the peripheral nervous system. Despite their importance in the developing animal, the signals responsible for their induction remain unknown. Using the placodal marker, sox3, we have shown that the same Fgf signaling required for otic vesicle development is required for the development of the epibranchial placodes. Loss of both Fgf3 and Fgf8 is sufficient to block placode development. We further show that epibranchial sox3 expression is unaffected in mutants in which no otic placode forms, where dlx3b and dlx4b are knocked down, or deleted along with sox9a. However, the forkhead factor, Foxi1, is required for both otic and epibranchial placode development. Thus, both the otic and epibranchial placodes form in a common region of ectoderm under the influence of Fgfs, but these two structures subsequently develop independently. Although previous studies have investigated the signals that trigger neurogenesis from the epibranchial placodes, this represents the first demonstration of the signaling events that underlie the formation of the placodes themselves, and therefore, the process that determines which ectodermal cells will adopt a neural fate.
- Published
- 2007
- Full Text
- View/download PDF
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