Targeted disruption of Hoxd9 and Hoxd10 alters locomotor behavior, vertebral identity, and peripheral nervous system development.
The five most 5' HoxD genes, which are related to the Drosophila Abd-B gene, play an important role in patterning axial and appendicular skeletal elements and the nervous system of developing vertebrate embryos. Three of these genes, Hoxd11, Hoxd12, and Hoxd13, act synergistically to pattern the hindlimb autopod. In this study, we examine the combined effects of two additional 5' HoxD genes, Hoxd9 and Hoxd10. Both of these genes are expressed posteriorly in overlapping domains in the developing neural tube and axial mesoderm as well as in developing limbs. Locomotor behavior in animals carrying a double mutation in these two genes was altered; these alterations included changes in gait, mobility, and adduction. Morphological analysis showed alterations in axial and appendicular skeletal structure, hindlimb peripheral nerve organization and projection, and distal hindlimb musculature. These morphological alterations are likely to provide the substrate for the observed alterations in locomotor behavior. The alterations observed in double-mutant mice are distinct from the phenotypes observed in mice carrying single mutations in either gene, but exhibit most of the features of both individual phenotypes. This suggests that the combined activity of two adjacent Hox genes provides more patterning information than activity of each gene alone. These observations support the idea that adjacent Hox genes with overlapping expression patterns may interact functionally to provide patterning information to the same regions of developing mouse embryos.
de la Cruz
C C
CC
Department of Psychiatry, University of California at Los Angeles School of Medicine 90024, USA.
Der-Avakian
A
A
Spyropoulos
D D
DD
Tieu
D D
DD
Carpenter
E M
EM
D000818:Animals; D019521:Body Patterning; D004268:DNA-Binding Proteins / Q000235:genetics*; D005684:Gait / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D018390:Gene Targeting; D006614:Hindlimb / Q000196:embryology / Q000294:innervation; D018398:Homeodomain Proteins / Q000235:genetics*; D007150:Immunohistochemistry; D017880:Limb Deformities, Congenital / Q000235:genetics; D008124:Locomotion / Q000235:genetics*; D051379:Mice; D016296:Mutagenesis; D009363:Neoplasm Proteins / Q000235:genetics*; D017933:Peripheral Nervous System / Q000196:embryology*; D013127:Spinal Nerves / Q000196:embryology; D013131:Spine / Q000002:abnormalities / Q000196:embryology; D014157:Transcription Factors / Q000235:genetics*; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C490944:Hoxd10 protein, mouse; C489520:Hoxd4 protein, mouse; C490282:Hoxd9 protein, mouse; D009363:Neoplasm Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C099223:hoxd10a protein, zebrafish