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First published online February 18, 2004
doi: 10.1242/10.1242/dev.01024

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Gata2 specifies serotonergic neurons downstream of sonic hedgehog

¹ Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA
² Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109, USA
³ Rinat Neuroscience, 3155 Porter Drive, Palo Alto, California 94304, USA

^* Author for correspondence (e-mail: craven{at}gene.com)

Accepted 9 December 2003

Distinct classes of serotonergic (5-HT) neurons develop along the ventral midline of the vertebrate hindbrain. Here, we identify a Sonic hedgehog (Shh)-regulated cascade of transcription factors that acts to generate a specific subset of 5-HT neurons. This transcriptional cascade is sufficient for the induction of rostral 5-HT neurons within rhombomere 1 (r1), which project to the forebrain, but not for the induction of caudal 5-HT neurons, which largely terminate in the spinal cord. Within the rostral hindbrain, the Shh-activated homeodomain proteins Nkx2.2 and Nkx6.1 cooperate to induce the closely related zinc-finger transcription factors Gata2 and Gata3. Gata2 in turn is necessary and sufficient to activate the transcription factors Lmx1b and Pet1, and to induce 5-HT neurons within r1. In contrast to Gata2, Gata3 is not required for the specification of rostral 5-HT neurons and appears unable to substitute for the loss of Gata2. Our findings reveal that the identity of closely related 5-HT subclasses occurs through distinct responses of adjacent rostrocaudal progenitor domains to broad ventral inducers.

Key words: Gata, Serotonergic neurons, Sonic hedgehog

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