The paralogous Hox genes Hoxa10 and Hoxd10 interact to pattern the mouse hindlimb peripheral nervous system and skeleton.
The most 5' mouse Hoxa and Hoxd genes, which occupy positions 9-13 and which are related to the Drosophila AbdB gene, are all active in patterning developing limbs. Inactivation of individual genes produces alterations in skeletal elements of both forelimb and hindlimb; inactivation of some of these genes also alters hindlimb innervation. Simultaneous inactivation of paralogous or nonparalogous Hoxa and Hoxd genes produces more widespread alterations, suggesting that combinatorial interactions between these genes are required for proper limb patterning. We have examined the effects of simultaneous inactivation of Hoxa10 and Hoxd10 on mouse hindlimb skeletal and nervous system development. These paralogous genes are expressed at lumbar and sacral levels of the developing neural tube and surrounding axial mesoderm as well as in developing forelimb and hindlimb buds. Double-mutant animals demonstrated impaired locomotor behavior and altered development of posterior vertebrae and hindlimb skeletal elements. Alterations in hindlimb innervation were also observed, including truncations and deletions of the tibial and peroneal nerves. Animals carrying fewer mutant alleles show similar, but less extreme phenotypes. These observations suggest that Hoxa10 and Hoxd10 coordinately regulate skeletal development and innervation of the hindlimb.
Wahba
G M
GM
Mental Retardation Research Center, Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, 760 Westwood Plaza, Los Angeles, California 90024, USA.
Hostikka
S L
SL
Carpenter
E M
EM
D000818:Animals; D001846:Bone Development; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D006614:Hindlimb / Q000196:embryology* / Q000294:innervation*; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D009043:Motor Activity; D010525:Peripheral Nerves / Q000196:embryology*; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; C490944:Hoxd10 protein, mouse; C489520:Hoxd4 protein, mouse; D014157:Transcription Factors; D029961:Zebrafish Proteins; C099223:hoxd10a protein, zebrafish; C092119:Hoxa10 protein, mouse