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First published online 29 March 2006
doi: 10.1242/dev.02326

Development 133, 1779-1787 (2006)
Published by The Company of Biologists 2006
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Sp8 controls the anteroposterior patterning at the midbrain-hindbrain border

Gundula Griesel1, Dieter Treichel1, Patrick Collombat1, Jens Krull1, Andreas Zembrzycki1, Willem M. R. van den Akker1,2, Peter Gruss1, Antonio Simeone3,4,5 and Ahmed Mansouri1,6,*,{dagger}

1 Max-Planck Institute for Biophysical Chemistry, Dept of Molecular Cell Biology, am Fassberg, 37077 Göttingen, Germany.
2 Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
3 Ceinge Biotecnologie Avanzate and SEMM European School of Molecular Medicine-Naples site, Via Comunale Margherita 482, 80145 Naples, Italy.
4 MRC Centre for Developmental Neurobiology, New Hunt's House, 4th Floor, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK.
5 Institute of Genetics and Biophysics `A. Buzzati-Traverso', CNR, Via P. Castellino 111, 80131 Naples.
6 Clininal Neurophysiology, University of Göttingen, Robert-Koch-strasse 40, 37075 Göttingen, Germany.

{dagger} Author for correspondence (e-mail: amansou{at}gwdg.de)

Accepted 13 March 2006

The specification of neuronal cell types in the developing neural tube is orchestrated by signaling centers. However, how patterned territories of the central nervous system (CNS) are organized into structures with appropriate size and shape is still unclear. We report that in the absence of the mouse transcription factor mBtd/Sp8, a posterior shift of the isthmic organizer (IsO) occurs, suggesting a crucial role for Sp8 in this process. In addition, large patches of cells ectopically expressing Fgf8, Otx2 and/or Wnt1 in the rostral hindbrain are detected in Sp8 mutant embryos. In this context, midbrain dopaminergic neurons are found posterior to the IsO. Furthermore, we provide evidence that cell proliferation in the mid- and hindbrain is tightly controlled by Sp8 activity. Our observations are consistent with a role for Sp8 in restricting Fgf8 expression at the IsO.

Key words: Sp8 (mBtd), Isthmic organizer, Midbrain, AP patterning, Mouse






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