Article abstract
Nature Neuroscience 12, 1373 - 1380 (2009)
Published online: 18 October 2009 | doi:10.1038/nn.2409
Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors
Eve Seuntjens1,2,5, Anjana Nityanandam3,5, Amaya Miquelajauregui3, Joke Debruyn1,2, Agata Stryjewska1,2, Sandra Goebbels3, Klaus-Armin Nave3, Danny Huylebroeck1,2 & Victor Tarabykin3,4
Abstract
The fate of cortical progenitors, which progressively generate neurons and glial cells during development, is determined by temporally and spatially regulated signaling mechanisms. We found that the transcription factor Sip1 (Zfhx1b), which is produced at high levels in postmitotic neocortical neurons, regulates progenitor fate non–cell autonomously. Conditional deletion of Sip1 in young neurons induced premature production of upper-layer neurons at the expense of deep layers, precocious and increased generation of glial precursors, and enhanced postnatal astrocytogenesis. The premature upper-layer generation coincided with overexpression of the neurotrophin-3 (Ntf3) gene and upregulation of fibroblast growth factor 9 (Fgf9) gene expression preceded precocious gliogenesis. Exogenous application of Fgf9 to mouse cortical slices induced excessive generation of glial precursors in the germinal zone. Our data suggest that Sip1 restrains the production of signaling factors in postmitotic neurons that feed back to progenitors to regulate the timing of cell fate switch and the number of neurons and glial cells throughout corticogenesis.
- Laboratory of Molecular Biology (Celgen), Centre for Human Genetics, KULeuven, Leuven, Belgium.
- Department of Molecular and Developmental Genetics (VIB11), Flanders Institute for Biotechnology, Leuven, Belgium.
- Max-Planck-Institute for Experimental Medicine, Göttingen, Germany.
- Institute of Cell Biology and Neurobiology Charité–Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
- These authors contributed equally to this work.
Correspondence to: Danny Huylebroeck1,2 e-mail: danny.huylebroeck@med.kuleuven.be
Correspondence to: Victor Tarabykin3,4 e-mail: tarabykin@em.mpg.de
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