Hoxa10 and Hoxd10 coordinately regulate lumbar motor neuron patterning.

The paralogous Hox genes Hoxa10 and Hoxd10 are expressed in overlapping domains in the developing lumbar spinal cord and surrounding mesoderm. Independent inactivation of these two genes alters the trajectory of spinal nerves and decreases the complement of motor neurons present in the lumbar spinal cord, whereas dual inactivation of these two genes has been shown to alter peripheral nerve growth and development in the mouse hindlimb. We have examined the organization and distribution of lumbar motor neurons in the spinal cords of Hoxa10/Hoxd10 double mutant animals. Double mutant animals have decreased numbers of lumbar motor neurons in both the medial and lateral motor columns. The anteroposterior position of the lumbar motor column is shifted caudally in double mutant animals, and the distribution of motor neurons is altered across individual spinal segments. Distinctions between classes of motor neurons based on positional specificity appear disrupted in double mutants. Double mutants also demonstrate abnormal spinal cord vasculature and altered kidney placement and size. Our observations suggest that Hoxa10 and Hoxd10 activity is required to specify the position of the lumbar motor column and to provide segmental specification and identity for the lumbar motor neurons.