RRC ID 402
Author Norton WH, Mangoli M, Lele Z, Pogoda HM, Diamond B, Mercurio S, Russell C, Teraoka H, Stickney HL, Rauch GJ, Heisenberg CP, Houart C, Schilling TF, Frohnhoefer HG, Rastegar S, Neumann CJ, Gardiner RM, Strähle U, Geisler R, Rees M, Talbot WS, Wilson SW.
Title Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphé neurones and cranial motoneurones.
Journal Development
Abstract In this study, we elucidate the roles of the winged-helix transcription factor Foxa2 in ventral CNS development in zebrafish. Through cloning of monorail (mol), which we find encodes the transcription factor Foxa2, and phenotypic analysis of mol-/- embryos, we show that floorplate is induced in the absence of Foxa2 function but fails to further differentiate. In mol-/- mutants, expression of Foxa and Hh family genes is not maintained in floorplate cells and lateral expansion of the floorplate fails to occur. Our results suggest that this is due to defects both in the regulation of Hh activity in medial floorplate cells as well as cell-autonomous requirements for Foxa2 in the prospective laterally positioned floorplate cells themselves. Foxa2 is also required for induction and/or patterning of several distinct cell types in the ventral CNS. Serotonergic neurones of the raphenucleus and the trochlear motor nucleus are absent in mol-/- embryos, and oculomotor and facial motoneurones ectopically occupy ventral CNS midline positions in the midbrain and hindbrain. There is also a severe reduction of prospective oligodendrocytes in the midbrain and hindbrain. Finally, in the absence of Foxa2, at least two likely Hh pathway target genes are ectopically expressed in more dorsal regions of the midbrain and hindbrain ventricular neuroepithelium, raising the possibility that Foxa2 activity may normally be required to limit the range of action of secreted Hh proteins.
Volume 132(4)
Pages 645-58
Published 2005-2
DOI 10.1242/dev.01611
PII 132/4/645
PMID 15677724
PMC PMC2790417
MeSH Animals Central Nervous System / cytology Central Nervous System / embryology* Central Nervous System / physiology Embryo, Nonmammalian / cytology Embryo, Nonmammalian / metabolism Embryonic Induction / physiology* Forkhead Transcription Factors Gene Expression Regulation, Developmental / genetics Gene Expression Regulation, Developmental / physiology Hedgehog Proteins Motor Neurons / cytology* Motor Neurons / metabolism Mutation / genetics Oligodendroglia / cytology* Oligodendroglia / metabolism Raphe Nuclei / cytology Raphe Nuclei / embryology Raphe Nuclei / metabolism Serotonin / metabolism Trans-Activators / genetics Trans-Activators / metabolism Transcription Factors / genetics Transcription Factors / metabolism* Trochlear Nerve / cytology Trochlear Nerve / embryology Trochlear Nerve / metabolism Zebrafish / embryology Zebrafish / genetics Zebrafish / metabolism Zebrafish Proteins / genetics Zebrafish Proteins / metabolism*
IF 5.413
Times Cited 49
Zebrafish rw0