The vertebrate nervous system is one of the most complex organ systems in the entire animal kingdom. Its correct function relies on thousands of molecularly and functionally distinct neuronal cell types that need to be correctly specified and incorporated into neuronal circuits during development. Earlier work revealed that spatial signals control the specification of distinct classes of neurons, however, these signals are not sufficient to account for the full complexity of neurons – instead most neuronal classes can be further divided into distinct subtypes based on molecular and functional characteristics. Our recent work revealed a previously underappreciated temporal axis to neuronal subtype specification that further partitions the distinct classes of neurons into molecularly distinct subtypes. This program depends on cohorts of
transcription factors (TFs) that are specific for early, intermediate, or late-born neurons in large regions of the developing nervous system. This observation raises the exciting possibility that a shared temporal TF code orchestrates neuronal subtype specification in each neuronal class, which would elegantly explain how a large number of neuronal subtypes can be reproducibly specified at the right place, time, and quantity. The key aims of our research group are to:

1. Characterize the signals and transcriptional programmes orchestrating the temporal stratification of neurons in the spinal cord
2. Investigate how spatial and temporal TF programs cooperate to establish neuronal diversity
3. Delineate how temporal TF expression in the embryo underlies neuronal diversity and connectivity in the adult spinal cord

The expected results will provide a detailed understanding how spatial and temporal patterning systems jointly specify neuronal diversity and underlie the correct formation of neuronal circuitry in a vertebrate model system. In the long term, such mechanistic understanding of cell fate and connectivity may underpin the development of novel disease models and therapies for neurodegenerative movement disorders and spinal injuries