Partially Penetrant Cardiac Neural Crest Defects in Hand1 Phosphomutant Mice: Dimer Choice That Is Not So Critical

Beth A. Firulli, Anthony B. Firulli

Research output: Contribution to journalArticle


Hand1 is a basic Helix–loop–Helix transcription factor that exhibits post-translationally regulated dimer partner choice that allows for a diverse set of Hand1 transcriptional complexes. Indeed, when Hand1 phosphoregulation is altered, conditionally activated hypophorylation (Hand1PO4−) and phosphorylation mimic (Hand1PO4+) Hand1 alleles disrupt both craniofacial and limb morphogenesis with 100% penetrance. Interestingly, activation of conditional Hand1 Phosphomutant alleles within post-migratory neural crest cells produce heart defects that include ventricular septal defects, double-outlet right ventricle, persistent truncus arteriosus with partial penetrance. Single versus double-lobed thymus is a distinguishing feature between Wnt1-Cre;Hand1PO4−/+ and Wnt1-Cre;Hand1PO4+/+ mice. These data show that although Hand1 dimer regulation plays critical and consistent roles in disrupting craniofacial and limb morphogenesis, Hand1 dimer regulation during cardiac outflow track formation is less critical for normal morphogenesis. This review will present the OFT phenotypes observed in Hand1 Phosphomutant mice, and discuss possible mechanisms of how penetrance differences within the same tissues within the same embryos could be variable.

Original languageEnglish (US)
Pages (from-to)1339-1344
Number of pages6
JournalPediatric Cardiology
Issue number7
StatePublished - Oct 1 2019


  • Dimer regulation
  • Hand1
  • Post-translational modifications
  • bHLH

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Cardiology and Cardiovascular Medicine

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