Essential role of Gata transcription factors in sympathetic neuron development.
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.
Tsarovina
Konstantina
K
Max-Planck-Institut für Hirnforschung, Abteilung Neurochemie, Deutschordenstr. 46, 60528 Frankfurt/Main, Germany.
Pattyn
Alexandre
A
Stubbusch
Jutta
J
Müller
Frank
F
van der Wees
Jacqueline
J
Schneider
Carolin
C
Brunet
Jean-Francois
JF
Rohrer
Hermann
H
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002642:Chick Embryo; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D005726:Ganglia, Parasympathetic / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008125:Locus Coeruleus / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D013564:Sympathetic Nervous System / Q000196:embryology* / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins
D051792:Basic Helix-Loop-Helix Proteins; D019485:Bone Morphogenetic Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009638:Norepinephrine; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; C494712:Gata2 protein, mouse; C494748:Gata3 protein, mouse; C498766:Hand2 protein, mouse; C109220:NBPhox protein; C491060:Phox2a protein, mouse; C410915:hand2 protein, zebrafish