Retinoids and Spinal Cord Development

The role that RA plays in the development and patterning of the spinal cord is discussed. The morphogenetic process of neurulation is described in which RA plays a role because in the absence of RA signaling spina bifida results. Following neural induction, RA is involved in several patterning events in the spinal cord. It is one of the posteriorizing factors along with FGFs and Wnts and as such patterns the cervical spinal cord acting via the Hoxc transcription factors. It is involved in the induction of neural differentiation via genes such as NeuroM. It plays a part in patterning the dorsoventral axis of the anterior spinal cord where it interacts with FGF, Shh, and BMPs and induces an interneuronal population of neurons called V0 and V1 and a subset of motor neurons known as LMCs. To perform these actions RA is synthesized in the adjacent paraxial mesoderm by the enzyme RALDH2 and acts in a paracrine fashion on the developing neural tube. In the final action of RA, it begins to be synthesized within the neural tube at brachial and lumbar levels in the LMCs. Later-born neurons migrate through this RALDH2-expressing region and induce differentiation in these migrating neurons, which become a subset of LMC neurons known as LMCls. Thus RA acts several times over in the development of the spinal cord and not on the cells in which it is synthesized, but in adjacent cells in a paracrine manner.