SA1 Progenitor domains in the developing spinal cord: molecular control of neuronal diversity

The control of motor behaviour in the spinal cord depends on the coordinated activity of motor neurons (MN) and local circuit interneurons. Anatomical and physiological studies have revealed the existence of distinct classes of interneurons. They differ for their transcription factor profile, migration pattern, settling position and axonal trajectory, neurotransmitter phenotype and synaptic connectivity. During development distinct classes of interneurons are generated in a precise number and location in adjacent domains within the neural tube and subsequently are redistributed to their final destination by migration. Distinct neuronal identities are acquired through a progressive restriction in the developmental potential of progenitor cells in response to local environmental signals. In the last few years genetic and molecular approaches have begun to elucidate how these diverse aspects of interneuron phenotype emerge during development. Moreover, it has been possible to start to unravel the relationship between early genetic programs in progenitor cells and differentiated functions of interneuronal classes in the adult. We have shown that the spatially-restricted expression of a single progenitor HD protein, Dbx1, contributes to coordinate diverse phenotypic features that underlie interneuron identity and function within the developing spinal cord. These results begin to suggest a direct link between early programs of gene expression and differentiated features of interneuronal classes. In addition, they have allowed to genetically identify spinal interneurons that are involved in coordinating left-right motor activity during locomotion and, therefore, to relate early specification of neuronal identity with the formation of specific circuits in the mature spinal cord.