title: Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphé neurones and cranial motoneurones.
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.
authors.affiliation: Department of Anatomy and Developmental Biology, UCL, Gower Street, London WC1E 6BT, UK.
authors.forename: Will H
authors.initials: WH
authors.lastname: Norton
authors.forename: Maryam
authors.initials: M
authors.lastname: Mangoli
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Lele
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Pogoda
authors.forename: Brianne
authors.initials: B
authors.lastname: Diamond
authors.forename: Sara
authors.initials: S
authors.lastname: Mercurio
authors.forename: Claire
authors.initials: C
authors.lastname: Russell
authors.forename: Hiroki
authors.initials: H
authors.lastname: Teraoka
authors.forename: Heather L
authors.initials: HL
authors.lastname: Stickney
authors.forename: Gerd-Jörg
authors.initials: GJ
authors.lastname: Rauch
authors.forename: Carl-Philipp
authors.initials: CP
authors.lastname: Heisenberg
authors.forename: Corinne
authors.initials: C
authors.lastname: Houart
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Schilling
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Frohnhoefer
authors.forename: Sepand
authors.initials: S
authors.lastname: Rastegar
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Neumann
authors.forename: R Mark
authors.initials: RM
authors.lastname: Gardiner
authors.forename: Uwe
authors.initials: U
authors.lastname: Strähle
authors.forename: Robert
authors.initials: R
authors.lastname: Geisler
authors.forename: Michelle
authors.initials: M
authors.lastname: Rees
authors.forename: William S
authors.initials: WS
authors.lastname: Talbot
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Wilson
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004627:Embryonic Induction / Q000502:physiology*; D051858:Forkhead Transcription Factors; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D053823:Hedgehog Proteins; D009046:Motor Neurons / Q000166:cytology* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D011903:Raphe Nuclei / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014321:Trochlear Nerve / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051858:Forkhead Transcription Factors; D053823:Hedgehog Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; C082243:foxa2 protein, zebrafish; D012701:Serotonin