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First published online January 27, 2005
doi: 10.1242/10.1242/dev.01611

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Monorail/Foxa2 regulates floorplate differentiation and specification of oligodendrocytes, serotonergic raphé neurones and cranial motoneurones

Will H. Norton^1,, Maryam Mangoli^2,*,, Zsolt Lele^1,*,, Hans-Martin Pogoda^3,*, Brianne Diamond³, Sara Mercurio¹, Claire Russell¹, Hiroki Teraoka^1,¶, Heather L. Stickney³, Gerd-Jörg Rauch⁴, Carl-Philipp Heisenberg^1,**, Corinne Houart^1,, Thomas F. Schilling^1,, Hans-Georg Frohnhoefer⁴, Sepand Rastegar⁵, Carl J. Neumann, R. Mark Gardiner², Uwe Strähle⁶, Robert Geisler⁴, Michelle Rees^2,, William S. Talbot^3, and Stephen W. Wilson^1,

¹ Department of Anatomy and Developmental Biology, UCL, Gower Street, London WC1E 6BT, UK
² Department of Paediatrics and Child Health, Royal Free and University College Medical School, University College London, 5 University Street, London WC1E 6JJ, UK
³ Department of Developmental Biology, Stanford University School of Medicine, Beckman Center B315, 279 Campus Drive, Stanford, CA 94305-5329, USA
⁴ Department 3 - Genetics, Max-Planck-Institut für Entwicklungsbiologie, Spemannstrasse 35/III, D-72076 Tübingen, Germany
⁵ IGBMC, CNRS/INSERM/ULP, Parc d'Innovation, BP 10142, 67404 Illkirch Cedex, C.U. de Strasbourg, France
⁶ Universität Heidelberg und Institut für Toxikologie und Genetik, Forschungszentrum Karlsruhe, Postfach 3640, Germany

Authors for correspondence (e-mail: m.rees{at}ucl.ac.uk, talbot{at}cmgm.stanford.edu, s.wilson{at}ucl.ac.uk)

Accepted 29 November 2004

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 raphé nucleus 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.

Key words: Midline development, Hedgehog signalling, Zebrafish

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