Regionalized Twist1 activity in the forelimb bud drives the morphogenesis of the proximal and preaxial skeleton

David A F Loebel; Angelyn C C Hor; Heidi Bildsoe; Vanessa Jones; You-Tzung Chen; Richard R Behringer; Patrick P L Tam

doi:10.1016/j.ydbio.2011.11.020

Regionalized Twist1 activity in the forelimb bud drives the morphogenesis of the proximal and preaxial skeleton

Dev Biol. 2012 Feb 15;362(2):132-40. doi: 10.1016/j.ydbio.2011.11.020. Epub 2011 Dec 8.

Authors

David A F Loebel¹, Angelyn C C Hor, Heidi Bildsoe, Vanessa Jones, You-Tzung Chen, Richard R Behringer, Patrick P L Tam

Affiliation

¹ Embryology Unit, Children's Medical Research Institute, Sydney, Australia. [email protected]

PMID: 22178153
DOI: 10.1016/j.ydbio.2011.11.020

Abstract

Development of the mouse forelimb bud depends on normal Twist1 activity. Global loss of Twist1 function before limb bud formation stops limb development and loss of Twist1 throughout the mesenchyme after limb bud initiation leads to polydactyly, the ulnarization or loss of the radius and malformations and reductions of the shoulder girdle. Here we show that conditional deletion of Twist1 by Mesp1-Cre in the mesoderm that migrates into the anterior-proximal part of the forelimb bud results in the development of supernumerary digits and carpals, the acquisition of ulna-like characteristics by the radius and malformations of the humerus and scapula. The mirror-like duplications and posteriorization of pre-axial tissues are preceded by disruptions to anterior-posterior Shh, Bmp and Fgf signaling gradients and dysregulation of transcription factors that regulate anterior-posterior limb patterning.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / physiology
Basic Helix-Loop-Helix Transcription Factors / genetics
Basic Helix-Loop-Helix Transcription Factors / metabolism
Body Patterning / genetics*
Bone Morphogenetic Proteins / metabolism
Crosses, Genetic
DNA Primers / genetics
Fibroblast Growth Factors / metabolism
Fluorescent Antibody Technique
Forelimb / abnormalities*
Forelimb / embryology*
Forelimb / metabolism
Gene Deletion
Genotype
Hedgehog Proteins / metabolism
In Situ Hybridization
In Situ Nick-End Labeling
Mesoderm / metabolism
Mice
Mice, Inbred C57BL
Morphogenesis / genetics*
Morphogenesis / physiology
Nuclear Proteins / metabolism*
Signal Transduction / genetics*
Twist-Related Protein 1 / metabolism*
beta-Galactosidase

Substances

Basic Helix-Loop-Helix Transcription Factors
Bone Morphogenetic Proteins
DNA Primers
Hedgehog Proteins
Mesp1 protein, mouse
Nuclear Proteins
Shh protein, mouse
Twist-Related Protein 1
Twist1 protein, mouse
Fibroblast Growth Factors
beta-Galactosidase