Abstract

In many regions of the developing CNS, distinct cell types are born at different times. The means by which discrete and stereotyped temporal switches in cellular identities are acquired remains poorly understood. To address this, we have examined how visceral motor neurons (VMNs) and serotonergic neurons, two neuronal subtypes, are sequentially generated from a common progenitor pool in the vertebrate hindbrain. We found that the forkhead transcription factor Foxa2, acting in progenitors, is essential for the transition from VMN to serotonergic neurogenesis. Loss-of-function and gain-of-function experiments indicated that Foxa2 activates the switch through a temporal cross-repressive interaction with paired-like homeobox 2b (Phox2b), the VMN progenitor determinant. This mechanism bears a marked resemblance to the cross-repression between neighboring domains of transcription factors that establish discrete progenitor identities along the spatial axes. Moreover, the subsequent differentiation of central serotonergic neurons required both the suppression of VMN neurogenesis and the induction of downstream intrinsic determinants of serotonergic identity by Foxa2.

1. Developmental Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
2. National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK.
3. Centre National de la Recherche Scientifique UMR8542, Ecole Normale Supérieure, Département de Biologie, 46 Rue d'Ulm, 75005 Paris, France.
4. Developmental Biology Laboratory, Biomedical Research Foundation of the Academy of Athens, Soranou Ephessiou 4, Athens 11527, Greece.

Correspondence to: Siew-Lan Ang¹ e-mail: sang@nimr.mrc.ac.uk

Correspondence to: James Briscoe¹ e-mail: jbrisco@nimr.mrc.ac.uk

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