HOMEOTIC TRANSFORMATION OF CERVICAL-VERTEBRAE IN HOXA-4 MUTANT MICE

Hoxa-4 (previously known as Hox-1.4) is a mouse homeobox-containing ge ne that is expressed in the presumptive hindbrain and spinal cord, pre vertebrae, and other tissues during embryogenesis. To understand the r ole of Hoxa-4 during development, we generated Hoxa-4 mutant mice. Hom ozygous mutants were viable and fertile. Analysis of neonatal skeleton s revealed the development of ribs on the seventh cervical vertebra at variable penetrance and expressivity. A low frequency of alterations in sternal morphogenesis was also observed. In addition, we analyzed t he skeletons of transgenic mice that overexpress Hoxa-4 and found that the formation of the small rib anlagen that often develop on the seve nth cervical vertebra was suppressed. Analysis of adult homozyogus mut ant skeletons revealed that the dorsal process normally associated wit h the second cervical vertebra was also found on the third cervical ve rtebra. These results demonstrate that Hoxa-4 plays a role in conferri ng positional information along the anteroposterior axis to specify th e identity of the third and the seventh cervical vertebrae.