Ascl1/Mash1 is required for the development of central serotonergic neurons.
The transcriptional control of the differentiation of central serotonergic (5-HT) neurons in vertebrates has recently come under scrutiny and has been shown to involve the homeobox genes Nkx2-2 and Lmx1b, the Ets-domain gene Pet1 (also known as Fev) and the zinc-finger gene Gata3. The basic helix-loop-helix (bHLH) gene Ascl1 (also known as Mash1) is coexpressed with Nkx2-2 in the neuroepithelial domain of the hindbrain, which gives rise to 5-HT neurons. Here we show in the mouse that Ascl1 is essential for the birth of 5-HT neurons, both as a proneural gene for the production of postmitotic neuronal precursors and as a determinant of the serotonergic phenotype for the parallel activation of Gata3, Lmx1b and Pet1. Thus Ascl1, which is essential for noradrenergic differentiation, is also a determinant of the serotonergic phenotype.
Pattyn
Alexandre
A
CNRS UMR 8542, Ecole Normale Supérieure, 75005 Paris, France.
Simplicio
Nicolas
N
van Doorninck
J Hikke
JH
Goridis
Christo
C
Guillemot
François
F
Brunet
Jean-François
JF
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D000090322:Homeobox Protein Nkx-2.2; D051379:Mice; D008817:Mice, Mutant Strains; D009474:Neurons / Q000378:metabolism*; D012249:Rhombencephalon / Q000196:embryology* / Q000378:metabolism*; D012701:Serotonin / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D000090322:Homeobox Protein Nkx-2.2; D012701:Serotonin; D014157:Transcription Factors; C499317:Ascl1 protein, mouse; C000715627:Nkx2-2 protein, mouse