Hand1 phosphoregulation within the distal arch neural crest is essential for craniofacial morphogenesis

Beth A. Firulli, Robyn K. Fuchs, Joshua W. Vincentz, David E. Clouthier, Anthony B. Firulli

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

In this study we examine the consequences of altering Hand1 phosphoregulation in the developing neural crest cells (NCCs) of mice. Whereas Hand1 deletion in NCCs reveals a nonessential role for Hand1 in craniofacial development and embryonic survival, altering Hand1 phosphoregulation, and consequently Hand1 dimerization affinities, in NCCs results in severe mid-facial clefting and neonatal death.Hand1phosphorylation mutants exhibit a noncell-autonomous increase in pharyngeal arch cell death accompanied by alterations in Fgf8 and Shhpath way expression. Together, our data indicate that the extreme distal pharyngeal arch expression domain of Hand1 defines a novel bHLH-dependent activity, and that disruption of established Hand1 dimer phosphoregulation within this domain disrupts normal craniofacial patterning.

Original languageEnglish (US)
Pages (from-to)3050-3061
Number of pages12
JournalDevelopment (Cambridge)
Volume141
Issue number15
DOIs
StatePublished - Aug 2014

Keywords

  • bHLH
  • Craniofacial development
  • Dimerization
  • Hand1
  • Neural crest
  • Phosphorylation
  • Transcription

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

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