To BMP or not to BMP during vertebrate limb bud development

•The BMP pathway is part of the self-regulatory limb bud signaling system.•The highly dynamic BMP activity is regulated by the BMP antagonist Gremlin1.•High BMP is required during limb bud initiation, low activity for outgrowth.•Timely initiation of chondrogenesis depends on a renewed rise in BMP ac...

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Bibliographic Details
Published in:Seminars in cell & developmental biology 2014-08, Vol.32, p.119-127
Main Authors: Pignatti, Emanuele, Zeller, Rolf, Zuniga, Aimée
Format: Article
Language:English
Subjects:
Animals
Antagonist
BMP
Bone Morphogenetic Proteins - genetics
Bone Morphogenetic Proteins - metabolism
Gene Expression Regulation, Developmental
Limb bud
Limb Buds - embryology
Limb Buds - growth & development
Mice
Models, Genetic
Mouse
Organogenesis - genetics
Organogenesis - physiology
Protein Isoforms - genetics
Protein Isoforms - metabolism
Signal Transduction - genetics
Signal Transduction - physiology
Signaling
TGFβ
Vertebrates
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Summary:•The BMP pathway is part of the self-regulatory limb bud signaling system.•The highly dynamic BMP activity is regulated by the BMP antagonist Gremlin1.•High BMP is required during limb bud initiation, low activity for outgrowth.•Timely initiation of chondrogenesis depends on a renewed rise in BMP activity.•Alterations of the BMP pathway in human congenital malformations affecting limbs. The analysis of vertebrate limb bud development provides insight of general relevance into the signaling networks that underlie the controlled proliferative expansion of large populations of mesenchymal progenitors, cell fate determination and initiation of differentiation. In particular, extensive genetic analysis of mouse and experimental manipulation of chicken limb bud development has revealed the self-regulatory feedback signaling systems that interlink the main morphoregulatory signaling pathways including BMPs and their antagonists. It this review, we showcase the key role of BMPs and their antagonists during limb bud development. This review provides an understanding of the key morphoregulatory interactions that underlie the highly dynamic changes in BMP activity and signal transduction as limb bud development progresses from initiation and setting-up the signaling centers to determination and formation of the chondrogenic primordia for the limb skeletal elements.
ISSN:1084-9521
1096-3634
DOI:10.1016/j.semcdb.2014.04.004