The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development

Dlx homeobox genes are mammalian homologs of the Drosophila Distal-less (Dll) gene. The Dlx/Dll gene family is of ancient origin and appears to play a role in appendage development in essentially all species in which it has been identified. In Drosophila, Dll is expressed in the distal portion of th...

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Bibliographic Details
Published in:Genes & development 2002-05, Vol.16 (9), p.1089-1101
Main Authors: Robledo, Raymond F, Rajan, Lakshmi, Li, Xue, Lufkin, Thomas
Format: Article
Language:English
Subjects:
Animals
Body Patterning - genetics
Cartilage - abnormalities
Cartilage - embryology
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Ear - abnormalities
Extremities - embryology
Facial Bones - embryology
Female
Foot Deformities, Congenital - genetics
Gene Expression Regulation, Developmental
Hand Deformities, Congenital - genetics
Hindlimb
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Mice
Mice, Mutant Strains
Mice, Transgenic
Osteogenesis - genetics
Research Paper
Skeleton
Stem Cells - physiology
Transcription Factors
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Summary:Dlx homeobox genes are mammalian homologs of the Drosophila Distal-less (Dll) gene. The Dlx/Dll gene family is of ancient origin and appears to play a role in appendage development in essentially all species in which it has been identified. In Drosophila, Dll is expressed in the distal portion of the developing appendages and is critical for the development of distal structures. In addition, human Dlx5 and Dlx6 homeobox genes have been identified as possible candidate genes for the autosomal dominant form of the split-hand/split-foot malformation (SHFM), a heterogeneous limb disorder characterized by missing central digits and claw-like distal extremities. Targeted inactivation of Dlx5 and Dlx6 genes in mice results in severe craniofacial, axial, and appendicular skeletal abnormalities, leading to perinatal lethality. For the first time, Dlx/Dll gene products are shown to be critical regulators of mammalian limb development, as combined loss-of-function mutations phenocopy SHFM. Furthermore, spatiotemporal-specific transgenic overexpression of Dlx5, in the apical ectodermal ridge of Dlx5/6 null mice can fully rescue Dlx/Dll function in limb outgrowth.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.988402