Ascl1 Balances Neuronal versus Ependymal Fate in the Spinal Cord Central Canal

Abstract

Summary: Generation of neuronal types at the right time, location, and number is essential for building a functional nervous system. Significant progress has been reached in understanding the mechanisms that govern neuronal diversity. Cerebrospinal fluid-contacting neurons (CSF-cNs), an intriguing spinal cord central canal population, are produced during advanced developmental stages, simultaneous with glial and ependymal cells. It is unknown how CSF-cNs are specified after the neurogenesis-to-gliogenesis switch. Here, we identify delayed Ascl1 expression in mouse spinal progenitors during the gliogenic phase as key in CSF-cN differentiation. With fate mappings and time-controlled deletions, we demonstrate that CSF-cNs derive from Ascl1-expressing cells and that Ascl1 triggers late neurogenesis in the amniote spinal cord. Ascl1 abrogation transforms prospective CSF-cN progenitors into ependymocytes. These results demonstrate that late spinal progenitors have the potential to produce neurons and that Ascl1 initiates CSF-cN differentiation, controlling the precise neuronal and nonneuronal composition of the spinal central canal. : Cerebrospinal fluid-contacting neurons (CSF-cNs) are produced during the gliogenic phase of spinal cord development. Di Bella et al. demonstrate that, in amniotes, CSF-cNs arise from late Ascl1-expressing cells, and this transcription factor controls their development at the expense of ependymal cells. Thus, Ascl1 confers neurogenic potential to late spinal progenitors. Keywords: late neurogenesis, transcription factor, spinal cord, central canal, CSF-contacting neurons, CSF-cN, Ascl1, ependymocytes, neural progenitor, neuron specification