Hoxc10 and Hoxd10 regulate mouse columnar, divisional and motor pool identity of lumbar motoneurons.
A central question in neural development is how the broad diversity of neurons is generated in the vertebrate CNS. We have investigated the function of Hoxc10 and Hoxd10 in mouse lumbar motoneuron development. We show that Hoxc10 and Hoxd10 are initially expressed in most newly generated lumbar motoneurons, but subsequently become restricted to the lateral division of the lateral motor column (lLMC). Disruption of Hoxc10 and Hoxd10 caused severe hindlimb locomotor defects. Motoneurons in rostral lumbar segments were found to adopt the phenotype of thoracic motoneurons. More caudally the lLMC and dorsal-projecting axons were missing, yet most hindlimb muscles were innervated. The loss of the lLMC was not due to decreased production of motoneuron precursors or increased apoptosis. Instead, presumptive lLMC neurons failed to migrate to their normal position, and did not differentiate into other motoneurons or interneurons. Together, these results show that Hoxc10 and Hoxd10 play key roles in establishing lumbar motoneuron columnar, divisional and motor pool identity.
Wu
Yuanyuan
Y
Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
Wang
Guoying
G
Scott
Sheryl A
SA
Capecchi
Mario R
MR
D000483:Alleles; D000818:Animals; D018507:Gene Expression Regulation, Developmental; D006614:Hindlimb / Q000196:embryology / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008159:Lumbar Vertebrae / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism*; D009132:Muscles / Q000196:embryology / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D018398:Homeodomain Proteins; C490944:Hoxd10 protein, mouse; D014157:Transcription Factors; C076138:Hox 3.6 protein, mouse