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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2008.09.005 Byline: Karen Weisinger (a), David G. Wilkinson (b), Dalit Sela-Donenfeld (a)(b) Keywords: Follistatin; BMP4; FGF3; Hindbrain; Rhombomere; Segmentation; Chick Abstract: A network of molecular interactions is required in the developing vertebrate hindbrain for the formation and anterior-posterior patterning of the rhombomeres. FGF signaling is required in this network to upregulate the expression of the Krox20 and Kreisler segmentation genes, but little is known of how FGF gene expression is regulated in the hindbrain. We show that the dynamic expression of FGF3 in chick hindbrain segments and boundaries is similar to that of the BMP antagonist, follistatin. Consistent with a regulatory relationship between BMP signaling and FGF3 expression, we find that an increase in BMP activity due to blocking of follistatin translation by morpholino antisense oligonucleotides or overexpression of BMP results in strong inhibition of FGF3 expression. Conversely, addition of follistatin leads to an increase in the level of FGF3 expression. Furthermore, the segmental inhibition of BMP activity by follistatin is required for the expression of Krox20, Hoxb1 and EphA4 in the hindbrain. In addition, we show that the maintenance of FGF3 gene expression requires FGF activity, suggestive of an autoregulatory loop. These results reveal an antagonistic relationship between BMP activity and FGF3 expression that is required for correct segmental gene expression in the chick hindbrain, in which follistatin enables FGF3 expression by inhibiting BMP activity. Author Affiliation: (a) Koret School of Veterinary Medicine, The Hebrew University, Faculty of Agriculture, Food and Environmental Quality Sciences, P.O. Box 12, Rehovot 76100, Israel (b) Division of Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK Article History: Received 17 January 2008; Revised 4 September 2008; Accepted 5 September 2008

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.dsr.2007.09.007 Byline: Sally Hunter (a), David Wilkinson (a), Essyllt Louarn (b), I. Nick McCave (c), Eelco Rohling (a), Dorrik A.V. Stow (a), Sheldon Bacon (a) Keywords: Deep western boundary current; Eirik Drift; Hydrography; Sedimentation Abstract: Growing interest in the dynamics and temporal variability of the deep western boundary current (DWBC) in the northern North Atlantic has led to numerous studies of the modern hydrography and palaeoceanography of this current system. The DWBC is fed by the two dense water-masses that spill over the Greenland-Iceland-Scotland Ridge; Denmark Strait Overflow Water (DSOW) and Iceland Scotland Overflow Water (ISOW). These overflows entrain ambient water masses, primarily Labrador Sea Water (LSW), as they cross the Iceland and Irminger Basins before merging in the vicinity of south-east Greenland. A number of studies have been performed around the Eirik Drift, located off the southern Greenland margin, downstream of this main merging point. However, the relationship between the DWBC and the associated sedimentation at this location has yet to be fully elucidated. New hydrographic data show that the current's main sediment load is carried by only one of its components, the DSOW. Seismic surveys and sediment cores confirm that Holocene sedimentation is limited to areas underlying the most offshore part of the current, where the hydrographic data show the highest concentration of DSOW. Active sedimentation through the Holocene therefore appears to have been controlled by proximity to the sediment-laden DSOW. Our interpretation of new and historic geostrophic transport and tracer data from transects around the southern Greenland margin also suggests that the DWBC undergoes significant growth through entrainment as it flows around the Eirik Drift. We attribute this to multiple strands of ISOW following different depth-dependent pathways between exiting the Charlie Gibbs Fracture Zone and joining the DWBC. Comparison of our new data with other modern hydrographic datasets reveals significant temporal variability in the DWBC, associated with variations in the position, structure and age since ventilation of the current in the vicinity of Eirik Drift. The complexity of the current dynamics in this area has implications for the interpretation of hydrographic and palaeoceanographic data. Author Affiliation: (a) National Oceanography Centre, Southampton, University of Southampton Waterfront Campus, European Way, Southampton SO14 3ZH, UK (b) Laboratoire de Chimie Marine, UMR CNRS 7144 Roscoff and Institut Universitaire Europeen de la Mer/UBO, Place Nicolas Copernie, 29280 Plouzane, France (c) Department of Earth Sciences, University of Cambridge, Downing Street, Cambridge CB2 3EQ, UK Article History: Received 29 March 2007; Revised 14 August 2007; Accepted 11 September 2007

Within the developing vertebrate head, the migration of neural tube-derived neural crest cells (NCCs) through the cranial mesenchyme is patterned into three streams, with mesenchyme adjacent to rhombomeres (r)3 and r5 maintained NCC-free. The receptor tyrosine kinase erbB4 is expressed within r3 and r5 and is required to maintain the r3-adjacent NCC-free zone in mouse embryos. In this study, we demonstrate that the extent of r3 involvement in patterning mouse NCC migration is restricted to the same dorsolateral region regulated by erbB4. In chick embryos, we show that erbB4 signaling similarly maintains the r3-adjacent NCC-free zone. However, although r5 expresses erbB4, this is insufficient to maintain the r3-adjacent NCC-free zone in grafting experiments where r5 replaced r3, indicating that erbB4 requires additional factors at the A-P level of r3 to pattern NCC migration. Furthermore, we show that the r5-adjacent NCC-free zone is maintained independently of r5, but requires surface ectoderm. Finally, we demonstrate that avian cranial surface ectoderm is patterned molecularly, with dorsolateral surface ectoderm at the levels of r2/3 and r7 expressing the sulfatase QSulfl in quail, or the orthologue Csulfl in chick. Aberrant NCC migration into r3-adjacent mesenchyme correlated with more focused QSulfl expression in r2/3 surface ectoderm. Keywords: Neural crest; erbB4; Mesenchyme; Quail Sulfl; Chick Sulfl; Surface ectoderm: Cell migration patterning

• Laparoscopic inguinal herniorrhaphy is associated with higher recurrence rates compared to open herniotomy. • Our laparoscopic herniotomy (LIH) cohort shows low recurrence (1%), despite risk factors. • Our data supports growing favourable evidence on laparoscopic sac division techniques. Recent evidence suggests simple laparoscopic inguinal herniorrhaphy is associated with higher rates of recurrence and testicular ascent. We instigated a standardised approach to laparoscopic inguinal herniotomy (LIH), with circumferential sac division and 'purse-string' closure (4/0 monofilament polypropylene). An active follow-up programme was pursued. We reviewed our outcomes of this technique and compared them to an open herniotomy (OIH) cohort. LIH patients were identified prospectively (2017–2021): OIH retrospectively from 2016. Risk factors for complications were defined: extremely to very preterm (< 32 weeks), emergency presentation with incarceration, and redo surgery for recurrence. Data are presented as median [IQR]. Comparisons used Fisher's exact and Mann-Whitney U tests: significance defined as p < 0.05. 192 inguinal herniae in 140 patients were included in the LIH group and 214 herniae in 179 patients in the OIH group. Groups were similar in age and gender. The LIH group had a significantly larger proportion of cases that were premature, had emergency surgery, or had redo surgery after previous OIH. Follow-up was 24.4 months [10.8–33.6] vs. 66.4 [64.5–68.5] (LIH vs. OIH). Hernia recurrence occurred in 2/192 (1.0%) vs. 4/214 (1.9%) (LIH vs. OIH), p = 0.69. There was one known case of testicular ascent after OIH but none in the LIH group. Recreation of the open herniotomy laparoscopically appears to confer excellent outcomes, with low rates of recurrence despite a high proportion of patients having known risk factors. Further long-term data on rates of testicular ascent after active follow-up are required. [ABSTRACT FROM AUTHOR]

Recent studies have implicated Eph-related receptor tyrosine kinases and their membrane-bound ligands in restricting or stimulating the movement of cells and axons. Members of these large families of receptors and ligands fall into two major binding specificity classes, in which the GPI-anchored subgroup of ligands can each bind to all members of a subgroup of receptors, whereas the transmembrane ligands interact with a distinct subgroup of receptors. Analysis of expression patterns is therefore important in order to understand which receptor-ligand interactions occur in vivo. We have cloned mouse orthologues of five members of the ligand family and analysed in detail their developmental expression, in comparison with each other, and with the receptor specificity class they can interact with. We find that B61, AL-1/RAGS, LERK4, and ELF-1, members of the GPI-anchored subgroup of ligands, have both distinct and overlapping aspects to their expression in early mesoderm, somites, and branchial arches; in complex, dynamic patterns in the limb; and in spatial domains and specific neurons in the CNS. Similarly, Elk-L is expressed in hindbrain segments, the roof plate, and floor plate, which overlaps with that of other transmembrane ligands, but has distinct expression in somites. The expression domains of ligands are complementary to those of the corresponding receptors in a number of tissues, including the midbrain, hindbrain, and differentiating limbs, consistent with potential roles in restricting cell movement. In addition, we find that there are some overlaps in expression of receptors and ligands, for example in somites and the early limb. Taken together with previous studies showing that Eph-related receptors also have distinct but overlapping expression patterns, these data indicate that each ligand may have stage- and tissue-specific interactions with an individual member or multiple members of the receptor family.