title: Regionalized Twist1 activity in the forelimb bud drives the morphogenesis of the proximal and preaxial skeleton.
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.
authors.affiliation: Embryology Unit, Children's Medical Research Institute, Sydney, Australia. dloebel@cmri.org.au
authors.forename: David A F
authors.initials: DA
authors.lastname: Loebel
authors.forename: Angelyn C C
authors.initials: AC
authors.lastname: Hor
authors.forename: Heidi
authors.initials: H
authors.lastname: Bildsoe
authors.forename: Vanessa
authors.initials: V
authors.lastname: Jones
authors.forename: You-Tzung
authors.initials: YT
authors.lastname: Chen
authors.forename: Richard R
authors.initials: RR
authors.lastname: Behringer
authors.forename: Patrick P L
authors.initials: PP
authors.lastname: Tam
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D019521:Body Patterning / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D003433:Crosses, Genetic; D017931:DNA Primers / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005552:Forelimb / Q000002:abnormalities* / Q000196:embryology* / Q000378:metabolism; D017353:Gene Deletion; D005838:Genotype; D053823:Hedgehog Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis / Q000235:genetics* / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D001616:beta-Galactosidase
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D005346:Fibroblast Growth Factors; D053823:Hedgehog Proteins; D009687:Nuclear Proteins; D051879:Twist-Related Protein 1; D001616:beta-Galactosidase; C101538:Mesp1 protein, mouse; C465570:Shh protein, mouse; C067250:Twist1 protein, mouse