Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphé neurones and cranial motoneurones.
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.
Norton
Will H
WH
Department of Anatomy and Developmental Biology, UCL, Gower Street, London WC1E 6BT, UK.
Mangoli
Maryam
M
Lele
Zsolt
Z
Pogoda
Hans-Martin
HM
Diamond
Brianne
B
Mercurio
Sara
S
Russell
Claire
C
Teraoka
Hiroki
H
Stickney
Heather L
HL
Rauch
Gerd-Jörg
GJ
Heisenberg
Carl-Philipp
CP
Houart
Corinne
C
Schilling
Thomas F
TF
Frohnhoefer
Hans-Georg
HG
Rastegar
Sepand
S
Neumann
Carl J
CJ
Gardiner
R Mark
RM
Strähle
Uwe
U
Geisler
Robert
R
Rees
Michelle
M
Talbot
William S
WS
Wilson
Stephen W
SW
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*
D051858:Forkhead Transcription Factors; D053823:Hedgehog Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; C082243:foxa2 protein, zebrafish; D012701:Serotonin