Smad signaling in the neural crest regulates cardiac outflow tract remodeling through cell autonomous and non-cell autonomous effects

Qunshan Jia, Bradley W. McDill, Song Zhe Li, Chuxia Deng, Ching-Pin Chang, Feng Chen

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Neural crest cells (NCCs) are indispensable for the development of the cardiac outflow tract (OFT). Here, we show that mice lacking Smad4 in NCCs have persistent truncus arteriosus (PTA), severe OFT cushion hypoplasia, defective OFT elongation, and mispositioning of the OFT. Cardiac NCCs lacking Smad4 have increased apoptosis, apparently due to decreased Msx1/2 expression. This contributes to the reduction of NCCs in the OFT. Unexpectedly, mutants have MF20-expressing cardiomyocytes in the splanchnic mesoderm within the second heart field (SHF). This may result from abnormal differentiation or defective recruitment of differentiating SHF cells into OFT. Alterations in Bmp4, Sema3C, and PlexinA2 signals in the mutant OFT, SHF, and NCCs, disrupt the communications among different cell populations. Such disruptions can further affect the recruitment of NCCs into the OFT mesenchyme, causing severe OFT cushion hypoplasia and OFT septation failure. Furthermore, these NCCs have drastically reduced levels of Ids and MT1-MMP, affecting the positioning and remodeling of the OFT. Thus, Smad-signaling in cardiac NCCs has cell autonomous effects on their survival and non-cell autonomous effects on coordinating the movement of multiple cell lineages in the positioning and the remodeling of the OFT.

Original languageEnglish (US)
Pages (from-to)172-184
Number of pages13
JournalDevelopmental Biology
Volume311
Issue number1
DOIs
StatePublished - Nov 1 2007
Externally publishedYes

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Neural Crest
Mesoderm
Persistent Truncus Arteriosus
Matrix Metalloproteinase 14
Viscera
Cell Lineage
Cardiac Myocytes
Cell Communication
Cell Survival
Apoptosis

Keywords

  • Congenital heart diseases
  • Neural crest
  • Outflow tract
  • Secondary heart field
  • Smad

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Smad signaling in the neural crest regulates cardiac outflow tract remodeling through cell autonomous and non-cell autonomous effects. / Jia, Qunshan; McDill, Bradley W.; Li, Song Zhe; Deng, Chuxia; Chang, Ching-Pin; Chen, Feng.

In: Developmental Biology, Vol. 311, No. 1, 01.11.2007, p. 172-184.

Research output: Contribution to journalArticle

Jia, Qunshan ; McDill, Bradley W. ; Li, Song Zhe ; Deng, Chuxia ; Chang, Ching-Pin ; Chen, Feng. / Smad signaling in the neural crest regulates cardiac outflow tract remodeling through cell autonomous and non-cell autonomous effects. In: Developmental Biology. 2007 ; Vol. 311, No. 1. pp. 172-184.
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