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Molecular Control of the Cardiac Neural Crest
Author(s) -
Labosky Patricia Ann,
Mundell Nathan A,
Nelms Brian L,
Pfaltzgraff Elise R
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.177.3
Subject(s) - truncus arteriosus , neural crest , pax3 , biology , transcription factor , gata6 , mutant , embryo , progenitor , progenitor cell , genetics , microbiology and biotechnology , gene , tetralogy of fallot , medicine , stem cell , heart disease
The transcription factor Foxd3 is an important early regulator of neural crest (NC) progenitor cell maintenance, and a NC‐specific deletion of Foxd3 results in normal septation of the outflow tract but abnormal, ectopic NC‐derived VSMC in the distal aorta. In contrast, deletion of the transcription factor Pax3 causes a severe persistant truncus arteriosus (PTA). Using a combination of classical mouse genetics with tissue specific mutations, we discovered a genetic interaction between Pax3 and Foxd3. Compound mutant embryos homozygous for a NC‐specific Foxd3 mutation and heterozygous for Pax3 have fully penetrant PTA, severe thymus hypoplasia and midgestation lethality. These compound mutant embryos have increased cell death of NC progenitors with a corresponding reduction of NC, with an almost complete absence of NC caudal to the first pharyngeal arch, including the cardiac NC. This genetic interaction implicates gene dosage‐sensitive roles for Foxd3 and Pax3 in cardiac NC. Foxd3 and Pax3 act together to affect survival and maintenance of cardiac NC progenitors. This work was supported by an NIH R01 HD36720 to PAL, an NIH F31NS065604 and an AHA Predoctoral Fellowship 0615209B to NAM, an AHA Postdoctoral Fellowship 0725615B to BLN and T32 HD007043 (supporting BLN), and T32 HD007502 (supporting ERP).