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Background: This study describes the 20-year experience of managing common arterial trunk (CAT) in a low-and-middle-income country and compares the early and medium-term outcomes following the transition from conduit to nonconduit repair at the Red Cross War Memorial Children's Hospital., Methods: Single-center retrospective study of consecutive patients aged less than 18 years who underwent repair of CAT from January 1999 to December 2018 at the Red Cross War Memorial Children's Hospital. Patients with interrupted aortic arch or previous pulmonary artery banding were excluded., Results: Fifty-four patients had CAT repair during the study period. Thirty-four (63.0%) patients had a conduit repair, and 20 (37.0%) patients had a nonconduit repair. There were two intraoperative deaths. Thirty-day in-hospital mortality was 22.2% (12/54). Overall, in-hospital mortality was 29.6% (16/54). Eight (21.1%) late mortalities were observed. The actuarial survival for the conduit group was 77.5%, 53.4%, and 44.5% at 6, 12, and 27 months, respectively, and the nonconduit group was 58.6% at six months. The overall freedom from reoperation between the conduit group and nonconduit group was 66.2% versus 86.5%, 66.2% versus 76.9%, and 29.8% versus 64.1% at 1, 2, and 8 years, respectively., Conclusions: The outcomes following the transition to nonconduit repair for CAT in a low- and middle-income setting appear to be encouraging. There was no difference in mortality between conduit and nonconduit repairs, and importantly the results suggest a trend toward lower reintervention rates., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Persistent truncus arteriosus (PTA) is a rare congenital heart malformation. A 4-year-old girl was diagnosed with type I PTA through echocardiography and confirmed by cardiac CTA., (© 2024 Wiley Periodicals LLC.)

In normal cardiovascular development in birds and mammals, the outflow tract of the heart is divided into two distinct channels to separate the oxygenated systemic blood flow from the deoxygenated pulmonary circulation. When the process of outflow tract septation fails, a single common outflow vessel persists resulting in a serious clinical condition known as persistent truncus arteriosus or common arterial trunk. In this chapter, we will review molecular pathways and the cells that are known to play a role in the formation and development of the outflow tract and how genetic manipulation of these pathways in animal models can result in common arterial trunk., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Introduction: Homografts and bovine jugular vein are the most commonly used conduits for right ventricular outflow tract reconstruction at the time of primary repair of truncus arteriosus., Methods: We reviewed all truncus patients from 1990 to 2020 in two mid-volume centers. Inclusion criteria were primary repair, age under one year, and implantation of either homograft or bovine jugular vein. Kaplan-Meier analysis was used to estimate survival, freedom from reoperation on right ventricular outflow tract, and freedom from right ventricular outflow tract reoperation or catheter intervention., Results: Seventy-three patients met the inclusion criteria, homografts were implanted in 31, and bovine jugular vein in 42. There was no difference in preoperative characteristics between the two groups. There were 25/73 (34%) early postoperative deaths and no late deaths. Follow-up for survivals was 17.5 (interquartile range 13.5) years for homograft group, and 11.5 (interquartile range 8.5) years for bovine jugular vein group (P=0.002). Freedom from reoperation on right ventricular outflow tract at one, five, and 10 years in the homograft group were 100%, 83%, and 53%; and in bovine jugular vein group, it was 100%, 85%, and 50% (P=0.79). There was no difference in freedom from reoperation or catheter intervention (P=0.32)., Conclusion: Bovine jugular vein was equivalent to homografts up to 10 years in terms of survival and freedom from right ventricular outflow tract reoperation or catheter intervention. The choice of either valved conduit did not influence the durability of the right ventricle-pulmonary artery conduit in truncus arteriosus.

We describe a neonate with a unique variant of truncus arteriosus with interrupted aortic arch, an absent ascending aorta, persistent right dorsal aorta, and an unusual brachiocephalic artery pattern in which all head and neck vessels were supplied from the ductal arch-descending aorta continuum. ( Level of Difficulty: Beginner. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Persistent truncus arteriosus (PTA) is an uncommon and complex congenital cardiac malformation accounting for about 1.2% of all congenital heart diseases (CHDs), which is caused by a deficiency in the embryonic heart outflow tract's (OFT) septation and remodeling. PDGFRα and PDGFRβ double knockout (DKO) in cardiac neural crest cells (CNCCs) has been reported to cause PTA, but the underlying mechanisms remain unclear. Here, we constructed a PTA mouse model with PDGFRα and PDGFRβ double knockout in Pax3 + CNCCs and described the condensation failure into OFT septum of CNCC-derived cells due to disturbance of cell polarity in the DKO group. In addition, we further explored the mechanism with single-cell RNA sequencing. We found that two main cell differentiation trajectories into vascular smooth muscle cells (VSMCs) from cardiomyocytes (CMs) and mesenchymal cells (MSs), respectively, were interrupted in the DKO group. The process of CM differentiation into VSMC stagnated in a transitional CM I-like state, which contributed to the failure of OFT remodeling and muscular septum formation. On the other hand, a Penk + transitional MS II cluster closely related to cell condensation into the OFT septum disappeared, which led to the OFT's septation absence directly. In conclusion, the disturbance of CNCC-derived cells caused by PDGFRα and PDGFRβ knockout can lead to the OFT septation disorder and the occurrence of PTA.

During cardiogenesis, the outflow tract undergoes a complicated morphogenesis, including the re-alignment of the great blood vessels, and the separation of aorta and pulmonary trunk. The deficiency of FGF8 in the morphogenesis of outflow tract has been well studied, however, the effect of over-dosed FGF8 on the development of outflow tract remains unknown. In this study, Rosa26R-Fgf8 knock-in allele was constitutively activated by Wnt1-cre transgene in the mouse neural crest cells presumptive for the endocardial cushion of outflow tract. Surprisingly, Wnt1-cre; Rosa26R-Fgf8 mouse embryos exhibited persistent truncus arteriosus and died prior to E15.5. The cardiac neural crest cells in Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus did not degenerate as in WT controls, but proliferated into a thickened endocardial cushion and then, blocked the blood outflow from cardiac chambers into the lungs, which resulted in the embryonic lethality. Although the spiral aorticopulmonary septum failed to form, the differentiaion of the endothelium and smooth muscle in the Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus were impacted little. However, lineage tracing assay showed that the neural crest derived cells aggregated in the cushion layer, but failed to differentiate into the endothelium of Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus. Further investigation displayed the reduced p-Akt and p-Erk immunostaining, and the decreased Bmp2 and Bmp4 transcription in the endothelium of Wnt1-cre; Rosa26R-Fgf8 truncus arteriosus. Our findings suggested that Fgf8 over-expression in cardiac neural crest impaired the formation of aorticopulmonary septum by suppressing the endothelial differentiation and stimulating the proliferation of endocardial cushion cells, which implicated a novel etiology of persistent truncus arteriosus.

Objectives: Persistent truncus arteriosus represents less than 3% of all congenital heart defects. We aim to analyze mid-term outcomes after primary Truncus arteriosus repair at different ages and to identify the risk factors contributing to mortality and the need for intervention after surgical repair., Methods: This retrospective cohort study included 36 children, underwent repair of Truncus arteriosus in the period from January 2011 to December 2018 in two institutions. We recorded the clinical and echocardiographic data for the patients preoperatively, early postoperative, 6 months postoperative, then every year until their last documented follow-up appointment., Results: Thirty-six patients had truncus arteriosus repair during the study period. Thirty-one patients had open sternum post-repair, and two patients required extracorporeal membrane oxygenation. Bleeding occurred in 15 patients (41.67%), and operative mortality occurred in 5 patients (14.7%). Patients with truncus arteriosus type 2 (p = 0.008) and 3 (p = 0.001) and who were ventilated preoperatively (p < 0.001) had a longer hospital stay. Surgical re-intervention was required in 8 patients (22.86%), and 11 patients (30.56%) had catheter-based reintervention. Freedom from reintervention was 86% at 1 year, 75% at 2 years and 65% at 3 years. Survival at 1 year was 81% and at 3 years was 76%. High postoperative inotropic score predicted mortality (p = 0.013)., Conclusion: Repair of the truncus arteriosus can be performed safely with low morbidity and mortality, both in neonates, infants, and older children. Re-intervention is common, preferably through a transcatheter approach.

The cardiac neural crest arises in the hindbrain, then migrates to the heart and contributes to critical structures, including the outflow tract septum. Chick cardiac crest ablation results in failure of this septation, phenocopying the human heart defect persistent truncus arteriosus (PTA), which trunk neural crest fails to rescue. Here, we probe the molecular mechanisms underlying the cardiac crest's unique potential. Transcriptional profiling identified cardiac-crest-specific transcription factors, with single-cell RNA sequencing revealing surprising heterogeneity, including an ectomesenchymal subpopulation within the early migrating population. Loss-of-function analyses uncovered a transcriptional subcircuit, comprised of Tgif1, Ets1, and Sox8, critical for cardiac neural crest and heart development. Importantly, ectopic expression of this subcircuit was sufficient to imbue trunk crest with the ability to rescue PTA after cardiac crest ablation. Together, our results reveal a transcriptional program sufficient to confer cardiac potential onto trunk neural crest cells, thus implicating new genes in cardiovascular birth defects., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Congenital heart diseases (CHDs) involving the outflow tract (OFT), such as persistent truncus arteriosus (PTA), lead to mortality and morbidity with implications not only in the heart, but also in the pulmonary vasculature. The mechanisms of pulmonary artery (PA) development and the etiologies underlying PA disorders associated with CHD remain poorly understood partly because of a specific marker for PA development is nonexistent. The three subtypes of inositol 1,4,5-trisphosphate receptors (IP 3 R1, 2, and 3) are intracellular Ca 2+ channels that are essential for many tissues and organs. We discovered that IP 3 R2 was expressed in the vasculature and heart during development using transgenic mice, in which a LacZ marker gene was knocked into the IP 3 R2 locus. Whole-mount and section LacZ staining showed that IP 3 R2-LacZ-positive cells were detectable exclusively in the smooth muscle cells, or tunica media, of PA, merging into αSMA-positive cells during development. Furthermore, our analyses suggested that IP 3 R2-LacZ positive PA smooth muscle layers gradually elongate from the central PA to the peripheral PAs from E13.5 to E18.5, supporting the distal angiogenesis theory for the development of PA, whereas IP 3 R2-LacZ was rarely expressed in smooth muscle cells in the pulmonary trunk. Crossing IP 3 R-LacZ mice with mice hypomorphic for Tbx1 alleles revealed that PTA of Tbx1 mutants may result from agenesis or hypoplasia of the pulmonary trunk; thus, the left and right central to peripheral PAs connect directly to the dorsal side of the truncus arteriosus in these mutants. Additionally, we found hypercellular interstitial mesenchyme and delayed maturation of the lung endoderm in the Tbx1 mutant lungs. Our study identifies IP 3 R2 as a novel marker for clear visualization of PA during development and can be utilized for studying cardiopulmonary development and disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The surgical management of severe truncal valvular dysfunction is still challenging in neonates with persistent truncus arteriosus. This report describes a 14-day-old neonate with severe truncal valve insufficiency successfully undergoing truncal valve repairs, and followed by valve replacement at the age of 4 years. The truncal valve was quadricuspid with two large and two small leaflets, and all leaflets had severe dysplastic and myxomatous changes. We performed leaflet extension and bicuspidization valvuloplasty for this valve. This patient obtained somatic growth for 4 years without heart failure symptoms, and safely underwent prosthetic valve replacement. This technique would be effective for truncal valve dysfunction in neonates as the life-saving and the bridging procedure to valve replacement.

Persistent truncus arteriosus (PTA) is a relatively uncommon congenital heart disease, accounting for approximately 0.7-1.4% of all congenital cardiac abnormalities worldwide. PTA is usually accompanied by a single semilunar valve, with leaflets ranging from one to six in number. However, absent semilunar valve (ASV) is rarely seen in PTA. Here, we report a case of prenatally diagnosed PTA accompanied by ASV (PTA-ASV) confirmed by postmortem autopsy.

We present a case of a 3-week-old boy with persistent truncus arteriosus associated with interrupted right aortic arch having an anomalous origin of the left vertebral artery from the ascending aorta.

Background: Proper development of the great vessels of the heart and septation of the cardiac outflow tract requires cardiac neural crest cells. These cells give rise to the parasympathetic cardiac ganglia, the smooth muscle layer of the great vessels, some cardiomyocytes, and the conotruncal cushions and aorticopulmonary septum of the outflow tract. Ablation of cardiac neural crest cells results in defective patterning of each of these structures. Previous studies have shown that targeted deletion of the forkhead transcription factor C2 (Foxc2), results in cardiac phenotypes similar to that derived from cardiac neural crest cell ablation., Results: We report that Foxc2 -/- embryos on the 129s6/SvEv inbred genetic background display persistent truncus arteriosus and hypoplastic ventricles before embryonic lethality. Foxc2 loss-of-function resulted in perturbed cardiac neural crest cell migration and their reduced contribution to the outflow tract as evidenced by lineage tracing analyses together with perturbed expression of the neural crest cell markers Sox10 and Crabp1. Foxc2 loss-of-function also resulted in alterations in PlexinD1, Twist1, PECAM1, and Hand1/2 expression in association with vascular and ventricular defects., Conclusions: Our data indicate Foxc2 is required for proper migration of cardiac neural crest cells, septation of the outflow tract, and development of the ventricles. Developmental Dynamics 247:1286-1296, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

The purpose of this report is to assess the mid- and long-term outcomes of right ventricular outflow tract (RVOT) reconstruction for children with persistent truncus arteriosus. Between September 2006 and 2016, 105 patients with persistent truncus arteriosus (PTA) received surgical treatment at Shanghai Children's Medical Center. Direct right ventricle-pulmonary artery anastomosis (pulmonary artery pull-down) was performed in 51 patients; a left auricle or pericardial conduit was inserted between the RVOT and pulmonary artery as a connection in 17 patients; heterograft (bovine jugular vein or Gore-tex) conduits and homograft conduits were used in 30 and 7 cases, respectively, to connect the distal pulmonary and right ventricle outflow tract; and pulmonary valve reconstruction was performed in 38 patients using a Gore-tex monocusp. There were six in-hospital deaths and one delayed death 5 months after operation. After a mean follow-up of 55.8 ± 16.5 months (6-113 months), 19 patients underwent reoperation (3 with pulmonary patch enlargement, 14 with conduit replacement and 2 with aortic valve replacement) 10-89 months after the first operation, with 1 hospital death. The actuarial survival rates were 94.2, 93.3 and 93.3% at 1, 5 and 10 years, respectively. Freedom from reoperation was 98.0, 87.8 and 82.7% at 1, 5 and 10 years, respectively. The follow-up variables included echocardiography, chest radiography, cardiac CT and cardiac function. At the last examination, most of the patients exhibited an improvement of New York Heart Association functional class from III or IV preoperatively to I or II at follow-up. Surgical treatment for PTA has an acceptable survival rate and satisfactory outcomes. Most patients exhibited an improvement in cardiac function during follow-up. Aortic arch deformity, truncal valvular regurgitation and long cardiopulmonary bypass time were regarded as risk factors for hospital mortality. Autologous tissue has a lower reoperation rate and better growth potential than extracardiac conduits. A monocusp valve effectively reduces pulmonary regurgitation in the early postoperative stage.

The embryonic process of forming a complex structure such as the heart remains poorly understood. Here, we show that Six2 marks a dynamic subset of second heart field progenitors. Six2-positive (Six2 + ) progenitors are rapidly recruited and assigned, and their descendants are allocated successively to regions of the heart from the right ventricle (RV) to the pulmonary trunk. Global ablation of Six2 + progenitors resulted in RV hypoplasia and pulmonary atresia. An early stage-specific ablation of a small subset of Six2 + progenitors did not cause any apparent structural defect at birth but rather resulted in adult-onset cardiac hypertrophy and dysfunction. Furthermore, Six2 expression depends in part on Shh signaling, and Shh deletion resulted in severe deficiency of Six2 + progenitors. Collectively, these findings unveil the chronological features of cardiogenesis, in which the mammalian heart is built sequentially by temporally distinct populations of cardiac progenitors, and provide insights into late-onset congenital heart disease., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

This case report describes the pathological findings of multiple congenital cardiac defects in a 2-year-old female Shetland pony with clinical signs of chronic respiratory distress. Persistent truncus arteriosus (PTA) type IV, interventricular septal defect, overriding aorta, pulmonary trunk agenesis, pulmonary arteries arising from the descending aorta, and compensatory right ventricular hypertrophy were observed.

Background: Retinoic acid (RA), the bioactive derivative of vitamin A, is essential for vertebrate heart development. Both excess and reduced RA signaling lead to cardiovascular malformations affecting the outflow tract (OFT). To address the cellular mechanisms underlying the effects of RA signaling during OFT morphogenesis, we used transient maternal RA supplementation to rescue the early lethality resulting from inactivation of the murine retinaldehyde dehydrogenase 2 (Raldh2) gene., Results: By embryonic day 13.5, all rescued Raldh2(-/-) hearts exhibit severe, reproducible OFT septation defects, although wild-type and Raldh2(+/-) littermates have normal hearts. Cardiac neural crest cells (cNCC) were present in OFT cushions of Raldh2(-/-) mutant embryos but ectopically located in the periphery of the endocardial cushions, rather than immediately underlying the endocardium. Excess mesenchyme was generated by Raldh2(-/-) mutant endocardium, which displaced cNCC derivatives from their subendocardial, medial position., Conclusions: RA signaling affects not only cNCC numbers but also their position relative to endocardial mesenchyme during the septation process. Our study shows that inappropriate coordination between the different cell types of the OFT perturbs its morphogenesis and leads to a severe congenital heart defect, persistent truncus arteriosus., (© 2015 Wiley Periodicals, Inc.)

Heart outflow tract septation in mouse embryos carrying mutations in retinoic acid receptor genes fails with complete penetrance. In this mutant background, ectopic TGFβ signaling in the distal outflow tract is responsible for septation failure, but it was uncertain what tissue was responsive to ectopic TGFβ and why this response interfered with septation. By combining RAR gene mutation with tissue-specific Cre drivers and a conditional type II TGFβ receptor (Tgfbr2) allele, we determined that ectopic activation of TGFβ signaling in the endocardium is responsible for septation defects. Ectopic TGFβ signaling results in ectopic mesenchymal transformation of the endocardium and thereby in improperly constituted distal OFT cushions. Our analysis highlights the interactions between myocardium, endocardium, and neural crest cells in outflow tract morphogenesis, and demonstrates the requirement for proper TGFβ signaling in outflow tract cushion organization and septation., (Copyright © 2015. Published by Elsevier Inc.)

Latent transforming growth factor-β binding protein-1 (LTBP-1) is an extracellular protein that is structurally similar to fibrillin and has an important role in controlling transforming growth factor-β (TGF-β) signaling by storing the cytokine in the extracellular matrix and by being involved in the conversion of the latent growth factor to its active form. LTBP-1 is found as both short (LTBP-1S) and long (LTBP-1L) forms, which are derived through the use of separate promoters. There is controversy regarding the importance of LTBP-1L, as Ltbp1L knockout mice showed multiple cardiovascular defects but the complete null mice did not. Here, we describe a third line of Ltbp1 knockout mice generated utilizing a conditional knockout strategy that ablated expression of both L and S forms of LTBP-1. These mice show severe developmental cardiovascular abnormalities and die perinatally; thus these animals display a phenotype similar to previously reported Ltbp1L knockout mice. We reinvestigated the other "complete" knockout line and found that these mice express a splice variant of LTBP-1L and, therefore, are not complete Ltbp1 knockouts. Our results clarify the phenotypes of Ltbp1 null mice and re-emphasize the importance of LTBP-1 in vivo., (Copyright © 2015. Published by Elsevier B.V.)

Background: Coronary anomalies are frequently associated with congenital cardiac defects. Accordingly, we tested the hypothesis that the development of the tunica media of coronary arteries/arterioles is compromised in mice with cardiac defects of the outflow tract (persistent truncus arteriosus, double outlet right ventricle and transposition of the great arteries) by studying hearts of G7-9 generation mice bred from mutagenized mice caused by N-ethyl-N-nitrosourea. Mice were studied at embryonic days E16.5, E17.5, and postnatal days 1 and 11. Data were based on immunohistochemistry of serial sections., Results: In 21 of 24 mice with outflow tract defects, the development of smooth muscle in arteries and arterioles was retarded; most commonly arterioles had an incomplete layer of smooth muscle or in a few instances, lacked a tunica media. In this model, an absence of a coronary ostium occurred in only 2 mice, indicating that the mechanisms underlying the formation of coronary ostia and the recruitment and differentiation of vascular smooth muscle differ. Coronary fistulas were present in 20% and dilated vessels in 30% of the hearts with cardiac defects., Conclusions: The data suggest that vascular smooth muscle recruitment and differentiation are not necessarily linked to other coronary anomalies, such as absence of a main coronary artery or branching patterns., (© 2014 Wiley Periodicals, Inc.)

Persistent Truncus Arteriosus (PTA) is an extremely rare defect accounting for under 1% of all congenital heart disease, and over 85% of patients succumb to heart failure in infancy. We report a case of van Praagh type A3 PTA, which represents its rarest variant and accounts for only 8-10% of all patients with PTA. The presence of ductal stenosis in such cases is further exceedingly rare., (Copyright © 2014 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Background: The heart develops under reduced and varying oxygen concentrations, yet there is little understanding of oxygen metabolism in the normal and mal-development of the heart. Here we used a novel reagent, the ODD-Luc hypoxia reporter mouse (oxygen degradation domain, ODD) of Hif-1α fused to Luciferase (Luc), to assay the activity of the oxygen sensor, prolyl hydroxylase, and oxygen reserve, in the developing heart. We tested the role of hypoxia-dependent responses in heart development by targeted inactivation of Hif-1α., Methods and Results: ODD-Luciferase activity was 14-fold higher in mouse embryonic day 10.5 (E10.5) versus adult heart and liver tissue lysates. ODD-Luc activity decreased in 2 stages, the first corresponding with the formation of a functional cardiovascular system for oxygen delivery at E15.5, and the second after birth consistent with complete oxygenation of the blood and tissues. Reduction of maternal inspired oxygen to 8% for 4 hours caused minimal induction of luciferase activity in the maternal tissues but robust induction in the embryonic tissues in proportion to the basal activity, indicating a lack of oxygen reserve, and corresponding induction of a hypoxia-dependent gene program. Bioluminescent imaging of intact embryos demonstrated highest activity in the outflow portion of the E13.5 heart. Hif-1α inactivation or prolonged hypoxia caused outflow and septation defects only when targeted to this specific developmental window., Conclusions: Low oxygen concentrations and lack of oxygen reserve during a critical phase of heart organogenesis may provide a basis for vulnerability to the development of common septation and conotruncal heart defects., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Neural crest cells (NCCs) are physically responsible for craniofacial skeleton formation, pharyngeal arch artery remodeling and cardiac outflow tract septation during vertebrate development. Cdc42 (cell division cycle 42) is a Rho family small GTP-binding protein that works as a molecular switch to regulate cytoskeleton remodeling and the establishment of cell polarity. To investigate the role of Cdc42 in NCCs during embryonic development, we deleted Cdc42 in NCCs by crossing Cdc42 flox mice with Wnt1-cre mice. We found that the inactivation of Cdc42 in NCCs caused embryonic lethality with craniofacial deformities and cardiovascular developmental defects. Specifically, Cdc42 NCC knockout embryos showed fully penetrant cleft lips and short snouts. Alcian Blue and Alizarin Red staining of the cranium exhibited an unfused nasal capsule and palatine in the mutant embryos. India ink intracardiac injection analysis displayed a spectrum of cardiovascular developmental defects, including persistent truncus arteriosus, hypomorphic pulmonary arteries, interrupted aortic arches, and right-sided aortic arches. To explore the underlying mechanisms of Cdc42 in the formation of the great blood vessels, we generated Wnt1Cre-Cdc42-Rosa26 reporter mice. By beta-galactosidase staining, a subpopulation of Cdc42-null NCCs was observed halting in their migration midway from the pharyngeal arches to the conotruncal cushions. Phalloidin staining revealed dispersed, shorter and disoriented stress fibers in Cdc42-null NCCs. Finally, we demonstrated that the inactivation of Cdc42 in NCCs impaired bone morphogenetic protein 2 (BMP2)-induced NCC cytoskeleton remodeling and migration. In summary, our results demonstrate that Cdc42 plays an essential role in NCC migration, and inactivation of Cdc42 in NCCs impairs craniofacial and cardiovascular development in mice., (© 2013 Elsevier Inc. All rights reserved.)