Pax6 defines the di-mesencephalic boundary by repressing En1 and Pax2.
Transcriptional factors and signaling molecules are responsible for regionalization of the central nervous system. In the early stage of neural development, Pax6 is expressed in the prosencephalon, while En1 and Pax2 are expressed in the mesencephalon. Here, we misexpressed Pax6 in the mesencephalon to elucidate the mechanism of the di-mesencephalic boundary formation. Histological analysis, expression patterns of diencephalic marker genes, and fiber trajectory of the posterior commissure indicated that Pax6 misexpression caused a caudal shift of the di-mesencephalic boundary. Pax6 repressed En1, Pax2 and other tectum (mesencephalon)-related genes such as En2, Pax5, Pax7, but induced Tcf4, a diencephalon marker gene. To know how Pax6 represses En1 and Pax2, we ectopically expressed a dominant-active or negative form of Pax6. The dominant-active form of Pax6 showed a similar but more severe phenotype than Pax6, while the dominant-negative form showed an opposite phenotype, suggesting that Pax6 acts as a transcriptional activator. Thus Pax6 may repress tectum-related genes by activating an intervening repressor. The results of misexpression experiments, together with normal expression patterns of Pax6, En1 and Pax2, suggest that repressive interaction between Pax6 and En1/Pax2 defines the di-mesencephalic boundary.
Matsunaga
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E
Department of Molecular Neurobiology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aoba-ku, Sendai 980-8575, Japan.
Araki
I
I
Nakamura
H
H
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D008636:Mesencephalon / Q000196:embryology*; D051379:Mice; D051762:PAX2 Transcription Factor; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D051820:TCF Transcription Factors; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D004268:DNA-Binding Proteins; C080330:En1 protein, mouse; D005136:Eye Proteins; D018398:Homeodomain Proteins; D051762:PAX2 Transcription Factor; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C497319:Pax2 protein, mouse; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D051820:TCF Transcription Factors; C544895:Tcf7l2 protein, mouse; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors