Partially Penetrant Cardiac Neural Crest Defects in Hand1 Phosphomutant Mice: Dimer Choice That Is Not So Critical
| Autor: | Anthony B. Firulli, Beth A. Firulli |
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| Rok vydání: | 2019 |
| Předmět: |
Transcription
Genetic Morphogenesis 030204 cardiovascular system & hematology Article Mice 03 medical and health sciences 0302 clinical medicine Basic Helix-Loop-Helix Transcription Factors Animals Humans Medicine Craniofacial Transcription factor Alleles Regulation of gene expression business.industry Gene Expression Regulation Developmental Neural crest Phenotype Penetrance Double Outlet Right Ventricle Cell biology 030228 respiratory system Neural Crest Pediatrics Perinatology and Child Health Cardiology and Cardiovascular Medicine business Limb morphogenesis |
| Zdroj: | Pediatr Cardiol |
| ISSN: | 1432-1971 0172-0643 |
| DOI: | 10.1007/s00246-019-02162-8 |
| Popis: | 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 (Hand1(PO4−)) and phosphorylation mimic (Hand1(PO4+)) 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 vs double lobed thymus is a distinguishing feature between Wnt1Cre;Hand1(PO4−/+) and Wnt1-Cre;Hand1(PO4+/+) mice. These data show that although Hand1 dimer regulation play 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. |
| Databáze: | OpenAIRE |
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