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 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.
Robledo
Raymond F
RF
Brookdale Center for Developmental and Molecular Biology, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Rajan
Lakshmi
L
Li
Xue
X
Lufkin
Thomas
T
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002356:Cartilage / Q000002:abnormalities / Q000196:embryology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004423:Ear / Q000002:abnormalities; D005121:Extremities / Q000196:embryology*; D005147:Facial Bones / Q000196:embryology*; D005260:Female; D005532:Foot Deformities, Congenital / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006228:Hand Deformities, Congenital / Q000235:genetics; D006614:Hindlimb; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D010012:Osteogenesis / Q000235:genetics; D012863:Skeleton; D013234:Stem Cells / Q000502:physiology; D014157:Transcription Factors
C100596:DLX5 protein, human; C491014:DLX6 protein, human; D004268:DNA-Binding Proteins; C501120:Dlx5 protein, mouse; C100597:Dlx6 protein, mouse; D018398:Homeodomain Proteins; C084119:MSX2 protein; D014157:Transcription Factors