Defective Hand1 phosphoregulation uncovers essential roles for Hand1 in limb morphogenesis.
Development
; 144(13): 2480-2489, 2017 07 01.
Article
em En
| MEDLINE
| ID: mdl-28576769
ABSTRACT
The morphogenesis of the vertebrate limbs is a complex process in which cell signaling and transcriptional regulation coordinate diverse structural adaptations in diverse species. In this study, we examine the consequences of altering Hand1 dimer choice regulation within developing vertebrate limbs. Although Hand1 deletion via the limb-specific Prrx1-Cre reveals a non-essential role for Hand1 in mouse limb morphogenesis, altering Hand1 phosphoregulation, and consequently Hand1 dimerization affinities, results in a severe truncation of proximal-anterior limb elements. Molecular analysis reveals a non-cell-autonomous mechanism that causes widespread cell death within the embryonic limb bud. In addition, we observe changes in proximal-anterior gene regulation, including a reduction in the expression of Irx3, Irx5, Gli3 and Alx4, all of which are upregulated in Hand2 limb conditional knockouts. A reduction of Hand2 and Shh gene dosage improves the integrity of anterior limb structures, validating the importance of the Twist-family bHLH dimer pool in limb morphogenesis.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Botões de Extremidades
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Fatores de Transcrição Hélice-Alça-Hélice Básicos
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Morfogênese
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article