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First published online 25 August 2004
doi: 10.1242/dev.01370

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Essential role of Gata transcription factors in sympathetic neuron development

Konstantina Tsarovina¹, Alexandre Pattyn², Jutta Stubbusch¹, Frank Müller¹, Jacqueline van der Wees³, Carolin Schneider^1,*, Jean-Francois Brunet² and Hermann Rohrer^1,

¹ Max-Planck-Institut für Hirnforschung, Abteilung Neurochemie, Deutschordenstr. 46, 60528 Frankfurt/Main, Germany
² CNRS UMR 8542, Département de Biologie, Ecole Normale Supérieure, 46 rue d'Ulm, 75005 Paris, France
³ Department of Cell Biology, Erasmus MC, PO Box 1738, 3000 DR Rotterdam, The Netherlands

Author for correspondence (e-mail: rohrer{at}mpih-frankfurt.mpg.de)

Accepted 20 July 2004

Sympathetic neurons are specified during their development from neural crest precursors by a network of crossregulatory transcription factors, which includes Mash1, Phox2b, Hand2 and Phox2a. Here, we have studied the function of Gata2 and Gata3 zinc-finger transcription factors in autonomic neuron development. In the chick, Gata2 but not Gata3 is expressed in developing sympathetic precursor cells. Gata2 expression starts after Mash1, Phox2b, Hand2 and Phox2a expression, but before the onset of the noradrenergic marker genes Th and Dbh, and is maintained throughout development. Gata2 expression is affected in the chick embryo by Bmp gain- and loss-of-function experiments, and by overexpression of Phox2b, Phox2a, Hand2 and Mash1. Together with the lack of Gata2/3 expression in Phox2b knockout mice, these results characterize Gata2 as member of the Bmp-induced cluster of transcription factors. Loss-of-function experiments resulted in a strong reduction in the size of the sympathetic chain and in decreased Th expression. Ectopic expression of Gata2 in chick neural crest precursors elicited the generation of neurons with a non-autonomic, Th-negative phenotype. This implies a function for Gata factors in autonomic neuron differentiation, which, however, depends on co-regulators present in the sympathetic lineage. The present data establish Gata2 and Gata3 in the chick and mouse, respectively, as essential members of the transcription factor network controlling sympathetic neuron development.

Key words: Autonomic, Ciliary, Cholinergic, Noradrenergic, Hand2 (dhand), Bmp, Phox2b, Gata2, Gata3, Chick, Mouse

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