Ventral migration of early-born neurons requires Dcc and is essential for the projections of primary afferents in the spinal cord.
Neuronal migration and lamina-specific primary afferent projections are crucial for establishing spinal cord circuits, but the underlying mechanisms are poorly understood. Here, we report that in mice lacking Dcc (deleted in colorectal cancer), some early-born neurons could not migrate ventrally in the spinal cord. Conversely, forced expression of Dcc caused ventral migration and prevented dorsolateral migration of late-born spinal neurons. In the superficial layer of the spinal cord of Dcc-/- mutants, mislocalized neurons are followed by proprioceptive afferents, while their presence repels nociceptive afferents through Sema3a. Thus, our study has shown that Dcc is a key molecule required for ventral migration of early-born neurons, and that appropriate neuronal migration is a prerequisite for, and coupled to, normal projections of primary afferents in the developing spinal cord.
Ding
Yu-Qiang
YQ
Department of Anesthesiology, School of Medicine, Washington University Pain Center, St Louis, MO 63110, USA.
Kim
Ji-Young
JY
Xu
Yong-Sheng
YS
Rao
Yi
Y
Chen
Zhou-Feng
ZF
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D000075389:DCC Receptor; D017930:Genes, Reporter; D051379:Mice; D009154:Mutation; D009475:Neurons, Afferent / Q000378:metabolism*; D011956:Receptors, Cell Surface; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501910:Dcc protein, mouse; D011956:Receptors, Cell Surface; D040121:Semaphorin-3A; D025521:Tumor Suppressor Proteins