Axial and appendicular skeletal transformations, ligament alterations, and motor neuron loss in Hoxc10 mutants

Department of Psychiatry and Biobehavioral Science, UCLA School of Medicine, Los Angeles, CA 90095, USA.
International journal of biological sciences (Impact Factor: 4.37). 02/2009; 5(5):397-410.
Source: PubMed

ABSTRACT Vertebrate Hox genes regulate many aspects of embryonic body plan development and patterning. In particular, Hox genes have been shown to regulate regional patterning of the axial and appendicular skeleton and of the central nervous system. We have identified patterning defects resulting from the targeted mutation of Hoxc10, a member of the Hox10 paralogous family. Hoxc10 mutant mice have skeletal transformations in thoracic, lumbar, and sacral vertebrae and in the pelvis, along with alterations in the bones and ligaments of the hindlimbs. These results suggest that Hoxc10, along with other members of the Hox10 paralogous gene family, regulates vertebral identity at the transition from thoracic to lumbar and lumbar to sacral regions. Our results also suggest a general role for Hoxc10 in regulating chondrogenesis and osteogenesis in the hindlimb, along with a specific role in shaping femoral architecture. In addition, mutant mice have a reduction in lumbar motor neurons and a change in locomotor behavior. These results suggest a role for Hoxc10 in generating or maintaining the normal complement of lumbar motor neurons.

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    • "Pbx roles in developmental programs as cell fate specification have long been considered primarily as those of Hox cofactors (reviewed in Moens and Selleri, 2006). However, misexpression or loss of Hox genes result in mild alterations of the pelvic girdle, including defects in mice misexpressing Hoxd12 in lateral plate derivatives (Knezevic et al., 1997); modest malformations of pelvic bones and sacrum in Hoxc10 mutants (Hostikka et al., 2009); and lack of uterosacral ligaments in Hoxa11 mutant mice (Connell et al., 2008). Therefore, it is unlikely that Pbx homeoproteins effect their roles in pelvis formation solely as Hox cofactors, suggesting instead cooperation with other proteins, e.g. "
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