Zebrafish Dmrta2 regulates neurogenesis in the telencephalon.
Although recent findings showed that some Drosophila doublesex and Caenorhabditis elegans mab-3 related genes are expressed in neural tissues during development, their functions have not been fully elucidated. Here, we isolated a zebrafish mutant, ha2, that shows defects in telencephalic neurogenesis and found that ha2 encodes Doublesex and MAB-3 related transcription factor like family A2 (Dmrta2). dmrta2 expression is restricted to the telencephalon, diencephalon and olfactory placode during somitogenesis. We found that the expression of the proneural gene, neurogenin1, in the posterior and dorsal region of telencephalon (posterior-dorsal telencephalon) is markedly reduced in this mutant at the 14-somite stage without any defects in cell proliferation or cell death. In contrast, the telencephalic expression of her6, a Hes-related gene that is known to encode a negative regulator of neurogenin1, expands dramatically in the ha2 mutant. Based on over-expression experiments and epistatic analyses, we propose that zebrafish Dmrta2 controls neurogenin1 expression by repressing her6 in the posterior-dorsal telencephalon. Furthermore, the expression domains of the telencephalic marker genes, foxg1 and emx3, and the neuronal differentiation gene, neurod, are downregulated in the ha2 posterior-dorsal telencephalon during somitogenesis. These results suggest that Dmrta2 plays important roles in the specification of the posterior-dorsal telencephalic cell fate during somitogenesis.
Department of Biological Science, Graduate School of Science, Hiroshima University, Kagamiyama 1-3-1, Higashi-Hiroshima, Hiroshima 739-8526 Japan.
Akio
A
Yoshizawa
Yoshinari
Y
Nakahara
Toshiaki
T
Izawa
Tohru
T
Ishitani
Makiko
M
Tsutsumi
Atsushi
A
Kuroiwa
Motoyuki
M
Itoh
Yutaka
Y
Kikuchi
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004843:Epistasis, Genetic; D005038:Ethylnitrosourea / Q000737:chemistry; D018507:Gene Expression Regulation, Developmental; D016296:Mutagenesis; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D055495:Neurogenesis / Q000235:genetics*; D013687:Telencephalon / Q000196:embryology* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005038:Ethylnitrosourea; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C426854:Her6 protein, zebrafish; C486539:dmrt2a protein, zebrafish; C486337:neurog1 protein, zebrafish