mTOR deletion in neural crest cells disrupts cardiac outflow tract remodeling and causes a spectrum of cardiac defects through the mTORC1 pathway

2021 ◽  
Author(s):  
Xuguang Nie ◽  
Christopher L. Ricupero ◽  
Kai Jiao ◽  
Peixin Yang ◽  
Jeremy J. Mao
Keyword(s):  
Neural Crest ◽  
Neural Crest Cells ◽  
Outflow Tract ◽  
Cardiac Defects ◽  
Mtorc1 Pathway ◽  
Cardiac Outflow

Pax3 is required for cardiac neural crest migration in the mouse: evidence from the splotch (Sp2H) mutant

Development ◽  
1997 ◽  
Vol 124 (2) ◽  
pp. 505-514 ◽  
Author(s):  
S.J. Conway ◽  
D.J. Henderson ◽  
A.J. Copp
Keyword(s):  
Neural Crest ◽  
Neural Tube ◽  
Neural Crest Cells ◽  
Outflow Tract ◽  
Avian Embryo ◽  
Cardiac Neural Crest ◽  
Branchial Arches ◽  
Aortic Arches ◽  
Cardiac Outflow

Neural crest cells originating in the occipital region of the avian embryo are known to play a vital role in formation of the septum of the cardiac outflow tract and to contribute cells to the aortic arches, thymus, thyroid and parathyroids. This ‘cardiac’ neural crest sub-population is assumed to exist in mammals, but without direct evidence. In this paper we demonstrate, using RT-PCR and in situ hybridisation, that Pax3 expression can serve as a marker of cardiac neural crest cells in the mouse embryo. Cells of this lineage were traced from the occipital neural tube, via branchial arches 3, 4 and 6, into the aortic sac and aorto-pulmonary outflow tract. Confirmation that these Pax3-positive cells are indeed cardiac neural crest is provided by experiments in which hearts were deprived of a source of colonising neural crest, by organ culture in vitro, with consequent lack of up-regulation of Pax3. Occipital neural crest cell outgrowths in vitro were also shown to express Pax3. Mutation of Pax3, as occurs in the splotch (Sp2H) mouse, results in development of conotruncal heart defects including persistent truncus arteriosus. Homozygotes also exhibit defects of the aortic arches, thymus, thyroid and parathyroids. Pax3-positive neural crest cells were found to emigrate from the occipital neural tube of Sp2H/Sp2H embryos in a relatively normal fashion, but there was a marked deficiency or absence of neural crest cells traversing branchial arches 3, 4 and 6, and entering the cardiac outflow tract. This decreased expression of Pax3 in Sp2H/Sp2H embryos was not due to down-regulation of Pax3 in neural crest cells, as use of independent neural crest markers, Hoxa-3, CrabpI, Prx1, Prx2 and c-met also revealed a deficiency of migrating cardiac neural crest cells in homozygous embryos. This work demonstrates the essential role of the cardiac neural crest in formation of the heart and great vessels in the mouse and, furthermore, shows that Pax3 function is required for the cardiac neural crest to complete its migration to the developing heart.

scholarly journals Cardiac Neural Crest Cells Provide New Insight into Septation of the Cardiac Outflow Tract: Aortic Sac to Ventricular Septal Closure

1998 ◽  
Vol 196 (2) ◽  
pp. 129-144 ◽  
Author(s):  
Karen Waldo ◽  
Sachiko Miyagawa-Tomita ◽  
Donna Kumiski ◽  
Margaret L. Kirby
Keyword(s):  
Neural Crest ◽  
Neural Crest Cells ◽  
Outflow Tract ◽  
Cardiac Neural Crest ◽  
Insight Into ◽  
Cardiac Outflow

scholarly journals Histone Deacetylase 3 Regulates Smooth Muscle Differentiation in Neural Crest Cells and Development of the Cardiac Outflow Tract

2011 ◽  
Vol 109 (11) ◽  
pp. 1240-1249 ◽  
Author(s):  
Nikhil Singh ◽  
Chinmay M. Trivedi ◽  
MinMin Lu ◽  
Shannon E. Mullican ◽  
Mitchell A. Lazar ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Neural Crest ◽  
Histone Deacetylase ◽  
Neural Crest Cells ◽  
Muscle Differentiation ◽  
Outflow Tract ◽  
Histone Deacetylase 3 ◽  
Smooth Muscle Differentiation ◽  
Cardiac Outflow

scholarly journals Mis-Expression of a Cranial Neural Crest Cell-Specific Gene Program in Cardiac Neural Crest Cells Modulates HAND Factor Expression, Causing Cardiac Outflow Tract Phenotypes

2020 ◽  
Vol 7 (2) ◽  
pp. 13
Author(s):  
Joshua W. Vincentz ◽  
David E. Clouthier ◽  
Anthony B. Firulli
Keyword(s):  
Cell Death ◽  
Transcription Factors ◽  
Neural Crest ◽  
Neural Crest Cells ◽  
Outflow Tract ◽  
Dependent Manner ◽  
Reporter Expression ◽  
Cardiac Neural Crest ◽  
Gene Regulatory ◽  
Cardiac Outflow

Congenital heart defects (CHDs) occur with such a frequency that they constitute a significant cause of morbidity and mortality in both children and adults. A significant portion of CHDs can be attributed to aberrant development of the cardiac outflow tract (OFT), and of one of its cellular progenitors known as the cardiac neural crest cells (NCCs). The gene regulatory networks that identify cardiac NCCs as a distinct NCC population are not completely understood. Heart and neural crest derivatives (HAND) bHLH transcription factors play essential roles in NCC morphogenesis. The Hand1PA/OFT enhancer is dependent upon bone morphogenic protein (BMP) signaling in both cranial and cardiac NCCs. The Hand1PA/OFT enhancer is directly repressed by the endothelin-induced transcription factors DLX5 and DLX6 in cranial but not cardiac NCCs. This transcriptional distinction offers the unique opportunity to interrogate NCC specification, and to understand why, despite similarities, cranial NCC fate determination is so diverse. We generated a conditionally active transgene that can ectopically express DLX5 within the developing mouse embryo in a Cre-recombinase-dependent manner. Ectopic DLX5 expression represses cranial NCC Hand1PA/OFT-lacZ reporter expression more effectively than cardiac NCC reporter expression. Ectopic DLX5 expression induces broad domains of NCC cell death within the cranial pharyngeal arches, but minimal cell death in cardiac NCC populations. This study shows that transcription control of NCC gene regulatory programs is influenced by their initial specification at the dorsal neural tube.

scholarly journals Sonic hedgehog is required for cardiac outflow tract and neural crest cell development

2005 ◽  
Vol 283 (2) ◽  
pp. 357-372 ◽  
Author(s):  
I. Washington Smoak ◽  
N.A. Byrd ◽  
R. Abu-Issa ◽  
M.M. Goddeeris ◽  
R. Anderson ◽  
...  
Keyword(s):  
Neural Crest ◽  
Sonic Hedgehog ◽  
Neural Crest Cell ◽  
Cell Development ◽  
Outflow Tract ◽  
Crest Cell ◽  
Cardiac Outflow
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