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Twist1 performs distinct spatio‐temporal functions in developing cardiac neural crest cells
Author(s) -
Vincentz Joshua Wayne,
Barnes Ralston,
Firulli Beth,
Spicer Douglas,
Firulli Anthony
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.lb23
Subject(s) - neural crest , biology , microbiology and biotechnology , cre recombinase , cranial neural crest , transcription factor , genetics , embryo , transgene , genetically modified mouse , gene
Although many cell types derive from neural crest cell (NCC) progenitors, the transcriptional programs that govern NCC fate choice are not well understood. Twist1 −/− mutant cardiac NCC (cNCC) display migratory and morphological defects. Within the aorticopulmonary cushions (APC), Twist1 −/− cNCC form abnormal cellular aggregations, or nodules, that express high levels of the related transcription factors Hand1 and Hand2 . To precisely examine Twist1 function during cNCC maturation, we conditionally inactivated Twist1 in NCC at specific stages of development using the Wnt1‐Cre , P0‐Cre , and Hand1 Cre alleles, which respectively express Cre recombinase in pre‐migratory, migratory, and post‐migratory cNCC. cNCC‐specific Twist1 ablation causes outflow tract defects, the penetrance and expressivity of which lessens the later Twist1 function is disrupted. However, NCC‐derived nodules are evident in all conditional knockouts (CKOs), regardless of the timing of Twist1 ablation. Expression analyses identified Twist1 CKO nodules as sympathetic neurons. Ectopic Twist1 expression in NCC using the conditionally activatable CAG‐CAT‐Twist1 and Wnt1‐Cre alleles revealed that, compared to control embryos, the Twist1 ‐overexpresser sympathetic chain contains fewer cells, from which TH expression is largely excluded. These data suggest that Twist1 represses NCC sympathoadrenal survival or differentiation.