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Essential mesenchymal role of small GTPase Rac1 in interdigital programmed cell death during limb development

Authors
Journal
Developmental Biology
0012-1606
Publisher
Elsevier
Publication Date
Volume
335
Issue
2
Identifiers
DOI: 10.1016/j.ydbio.2009.09.014
Keywords
  • Bone Morphogenetic Proteins
  • Conditional Knockout Mice
  • Limb Development
  • Programmed Cell Death
  • Rac1
  • Syndactyly
Disciplines
  • Biology

Abstract

Abstract Developing vertebrate limbs are often utilized as a model for studying pattern formation and morphogenetic cell death. Herein, we report that conditional deletion of Rac1, a member of the Rho family of proteins, in mouse limb bud mesenchyme led to skeletal deformities in the autopod and soft tissue syndactyly, with the latter caused by a complete absence of interdigital programmed cell death. Furthermore, the lack of interdigital programmed cell death and associated syndactyly was related to down-regulated gene expression of Bmp2, Bmp7, Msx1, and Msx2, which are known to promote apoptosis in the interdigital mesenchyme. Our findings from Rac1 conditional mutants indicate crucial roles for Rac1 in limb bud morphogenesis, especially interdigital programmed cell death.

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