Cardiovascular Development and the Colonizing Cardiac Neural Crest Lineage

Although it is well established that transgenic manipulation of mammalian neural crest-related gene expression and microsurgical removal of premigratory chicken and Xenopus embryonic cardiac neural crest progenitors results in a wide spectrum of both structural and functional congenital heart defect...

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Main Authors: Paige Snider, Michael Olaopa, Anthony B. Firulli, Simon J. Conway
Format: Article
Language:English
Published: Wiley 2007-01-01
Series:The Scientific World Journal
Online Access:http://dx.doi.org/10.1100/tsw.2007.189
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author Paige Snider
Michael Olaopa
Anthony B. Firulli
Simon J. Conway
author_facet Paige Snider
Michael Olaopa
Anthony B. Firulli
Simon J. Conway
author_sort Paige Snider
collection DOAJ
description Although it is well established that transgenic manipulation of mammalian neural crest-related gene expression and microsurgical removal of premigratory chicken and Xenopus embryonic cardiac neural crest progenitors results in a wide spectrum of both structural and functional congenital heart defects, the actual functional mechanism of the cardiac neural crest cells within the heart is poorly understood. Neural crest cell migration and appropriate colonization of the pharyngeal arches and outflow tract septum is thought to be highly dependent on genes that regulate cell-autonomous polarized movement (i.e., gap junctions, cadherins, and noncanonical Wnt1 pathway regulators). Once the migratory cardiac neural crest subpopulation finally reaches the heart, they have traditionally been thought to participate in septation of the common outflow tract into separate aortic and pulmonary arteries. However, several studies have suggested these colonizing neural crest cells may also play additional unexpected roles during cardiovascular development and may even contribute to a crest-derived stem cell population. Studies in both mice and chick suggest they can also enter the heart from the venous inflow as well as the usual arterial outflow region, and may contribute to the adult semilunar and atrioventricular valves as well as part of the cardiac conduction system. Furthermore, although they are not usually thought to give rise to the cardiomyocyte lineage, neural crest cells in the zebrafish (Danio rerio) can contribute to the myocardium and may have different functions in a species-dependent context. Intriguingly, both ablation of chick and Xenopus premigratory neural crest cells, and a transgenic deletion of mouse neural crest cell migration or disruption of the normal mammalian neural crest gene expression profiles, disrupts ventral myocardial function and/or cardiomyocyte proliferation. Combined, this suggests that either the cardiac neural crest secrete factor/s that regulate myocardial proliferation, can signal to the epicardium to subsequently secrete a growth factor/s, or may even contribute directly to the heart. Although there are species differences between mouse, chick, and Xenopus during cardiac neural crest cell morphogenesis, recent data suggest mouse and chick are more similar to each other than to the zebrafish neural crest cell lineage. Several groups have used the genetically defined Pax3 (splotch) mutant mice model to address the role of the cardiac neural crest lineage. Here we review the current literature, the neural crest-related role of the Pax3 transcription factor, and discuss potential function/s of cardiac neural crest-derived cells during cardiovascular developmental remodeling.
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spelling doaj-art-41cfcb5c8e2c4c49a072239b1382eb782025-02-03T06:01:53ZengWileyThe Scientific World Journal1537-744X2007-01-0171090111310.1100/tsw.2007.189Cardiovascular Development and the Colonizing Cardiac Neural Crest LineagePaige Snider0Michael Olaopa1Anthony B. Firulli2Simon J. Conway3Cardiovascular Development Group, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USACardiovascular Development Group, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USACardiovascular Development Group, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USACardiovascular Development Group, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USAAlthough it is well established that transgenic manipulation of mammalian neural crest-related gene expression and microsurgical removal of premigratory chicken and Xenopus embryonic cardiac neural crest progenitors results in a wide spectrum of both structural and functional congenital heart defects, the actual functional mechanism of the cardiac neural crest cells within the heart is poorly understood. Neural crest cell migration and appropriate colonization of the pharyngeal arches and outflow tract septum is thought to be highly dependent on genes that regulate cell-autonomous polarized movement (i.e., gap junctions, cadherins, and noncanonical Wnt1 pathway regulators). Once the migratory cardiac neural crest subpopulation finally reaches the heart, they have traditionally been thought to participate in septation of the common outflow tract into separate aortic and pulmonary arteries. However, several studies have suggested these colonizing neural crest cells may also play additional unexpected roles during cardiovascular development and may even contribute to a crest-derived stem cell population. Studies in both mice and chick suggest they can also enter the heart from the venous inflow as well as the usual arterial outflow region, and may contribute to the adult semilunar and atrioventricular valves as well as part of the cardiac conduction system. Furthermore, although they are not usually thought to give rise to the cardiomyocyte lineage, neural crest cells in the zebrafish (Danio rerio) can contribute to the myocardium and may have different functions in a species-dependent context. Intriguingly, both ablation of chick and Xenopus premigratory neural crest cells, and a transgenic deletion of mouse neural crest cell migration or disruption of the normal mammalian neural crest gene expression profiles, disrupts ventral myocardial function and/or cardiomyocyte proliferation. Combined, this suggests that either the cardiac neural crest secrete factor/s that regulate myocardial proliferation, can signal to the epicardium to subsequently secrete a growth factor/s, or may even contribute directly to the heart. Although there are species differences between mouse, chick, and Xenopus during cardiac neural crest cell morphogenesis, recent data suggest mouse and chick are more similar to each other than to the zebrafish neural crest cell lineage. Several groups have used the genetically defined Pax3 (splotch) mutant mice model to address the role of the cardiac neural crest lineage. Here we review the current literature, the neural crest-related role of the Pax3 transcription factor, and discuss potential function/s of cardiac neural crest-derived cells during cardiovascular developmental remodeling.http://dx.doi.org/10.1100/tsw.2007.189
spellingShingle Paige Snider
Michael Olaopa
Anthony B. Firulli
Simon J. Conway
Cardiovascular Development and the Colonizing Cardiac Neural Crest Lineage
The Scientific World Journal
title Cardiovascular Development and the Colonizing Cardiac Neural Crest Lineage
title_full Cardiovascular Development and the Colonizing Cardiac Neural Crest Lineage
title_fullStr Cardiovascular Development and the Colonizing Cardiac Neural Crest Lineage
title_full_unstemmed Cardiovascular Development and the Colonizing Cardiac Neural Crest Lineage
title_short Cardiovascular Development and the Colonizing Cardiac Neural Crest Lineage
title_sort cardiovascular development and the colonizing cardiac neural crest lineage
url http://dx.doi.org/10.1100/tsw.2007.189
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AT simonjconway cardiovasculardevelopmentandthecolonizingcardiacneuralcrestlineage