BMP receptor type IA in limb bud mesenchyme regulates distal outgrowth and patterning

Ovchinnikov, Dmitry A., Selever, Jennifer, Wang, Ying, Chen, You-Tzung, Mishina, Yuji, Martin, James F. and Behringer, Martin R. (2006) BMP receptor type IA in limb bud mesenchyme regulates distal outgrowth and patterning. Developmental Biology, 295 1: 103-115. doi:10.1016/j.ydbio.2006.03.013

Author Ovchinnikov, Dmitry A.
Selever, Jennifer
Wang, Ying
Chen, You-Tzung
Mishina, Yuji
Martin, James F.
Behringer, Martin R.
Title BMP receptor type IA in limb bud mesenchyme regulates distal outgrowth and patterning
Journal name Developmental Biology   Check publisher's open access policy
ISSN 0012-1606
Publication date 2006-07
Sub-type Article (original research)
DOI 10.1016/j.ydbio.2006.03.013
Volume 295
Issue 1
Start page 103
End page 115
Total pages 13
Place of publication San Diego, U.S.
Publisher Elsevier
Language eng
Subject 1101 Medical Biochemistry and Metabolomics
110314 Orthopaedics
111401 Foetal Development and Medicine
06 Biological Sciences
Abstract The mesenchyme of the developing vertebrate limb responds to inductive signals, giving rise to skeletal elements that define limb shape and size. Several signals emanate from the limb ectoderm and in particular from the specialized epithelium of the apical ectodermal ridge (AER), including three members of the bone morphogenetic protein (BMP) family of signaling molecules, BMP2, BMP4 and BMP7. Using the Cre/loxP system in mice, we rendered limb bud mesenchyme insensitive to BMP signals through the type I receptor, BMPR-IA. Conditional mutants had shortened limbs and almost complete agenesis of the autopod because of reduced cell proliferation. Reduced expression of downstream BMP signaling targets, Msx1, Msx2 and gremlin in the distal mesenchyme (progress zone) correlated with decreased levels of cyclin D1 and Wnt5a. Ectopic anterior activation of sonic hedgehog (SHH) signaling and Hox expression revealed alterations in anterior–posterior (AP) patterning. Abnormal localization of Lmx1b-expressing cells in the ventral mesenchyme, along with histological alterations and an abnormal melanization pattern of the limb, indicate altered dorsal–ventral (DV) boundaries. These findings suggest that signaling through BMPR-IA in limb mesenchyme is essential for distal outgrowth and also influences AP and DV patterning.
Keyword Bone morphogenetic protein receptor
Limb development
Pattern formation
Conditional knockout
References Bone morphogenetic protein receptor; Limb development; Pattern formation; Conditional knockout; Prx1
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Australian Institute for Bioengineering and Nanotechnology Publications
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