Sp8 is crucial for limb outgrowth and neuropore closure

AUTOR(ES)

Bell, Sheila M.

FONTE

National Academy of Sciences

RESUMO

In this report we describe the developmental expression and function of Sp8, a member of the Sp family of zinc finger transcription factors, and provide evidence that the legless transgene insertional mutant is a hypomorphic allele of the Sp8 gene. Sp8 is expressed during embryogenesis in the forming apical ectodermal ridge (AER), restricted regions of the central nervous system, and tail bud. Targeted deletion of the Sp8 gene gives a striking phenotype, with severe truncation of both forelimbs and hindlimbs, absent tail, as well as defects in anterior and posterior neuropore closure leading to exencephaly and spina bifida. Outgrowth of the limb depends on formation of the AER, a signaling center that forms at the limb bud apex. In Sp8 mutants, the AER precursor cells are induced and initially express multiple appropriate marker genes, but expression of these genes is not maintained and progression to a mature AER is blocked. These observations indicate that Sp8 functions downstream of Wnt3, Fgf10, and Bmpr1a in the signaling cascade that mediates AER formation.

Documentos Relacionados

• Fgfr2 is required for limb outgrowth and lung-branching morphogenesis
• Genomic structure and cloning of two transcript isoforms of human Sp8
• D-MANNOSE AS A CONSTITUENT OF THE DNA OF A MUTANT STRAIN OF BACTERIOPHAGE SP8
• A splice variant of CD44 expressed in the apical ectodermal ridge presents fibroblast growth factors to limb mesenchyme and is required for limb outgrowth
• The C Terminus of YopT Is Crucial for Activity and the N Terminus Is Crucial for Substrate Binding