Msx2 is an immediate downstream effector of Pax3 in the development of the murine cardiac neural crest

Stanford J. Kwang, Sean M. Brugger, Arthur Lazik, Amy E. Merrill, Lan Ying Wu, Yi Hsin Liu, Mamoru Ishii, Frank O. Sangiorgi, Michael Rauchman, Henry M. Sucov, Richard L. Maas, Robert E. Maxson

Research output: Contribution to journalReview articlepeer-review

77 Scopus citations

Abstract

The neural crest plays a crucial part in cardiac development. Cells of the cardiac subpopulation of cranial neural crest migrate from the hindbrain into the outflow tract of the heart where they contribute to the septum that divides the pulmonary and aortic channels. In Splotch mutant mice, which lack a functional Pax3 gene, migration of cardiac neural crest is deficient and aorticopulmonary septation does not occur. Downstream genes through which Pax3 regulates cardiac neural crest development are unknown. Here, using a combination of genetic and molecular approaches, we show that the deficiency of cardiac neural crest development in the Splotch mutant is caused by upregulation of Msx2, a homeobox gene with a well-documented role as a regulator of BMP signaling. We provide evidence, moreover, that Pax3 represses Msx2 expression via a direct effect on a conserved Pax3 binding site in the Msx2 promoter. These results establish Msx2 as an effector of Pax3 in cardiac neural crest development.

Original languageEnglish
Pages (from-to)527-538
Number of pages12
JournalDevelopment
Volume129
Issue number2
StatePublished - 2002

Keywords

  • Cardiac neural crest
  • Knockout
  • Mouse
  • Msx1
  • Msx2
  • Pax3
  • Splotch

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