title: Genetic activation of Hedgehog signaling unbalances the rate of neural stem cell renewal by increasing symmetric divisions.
abstract: In the adult brain, self-renewal is essential for the persistence of neural stem cells (NSCs) throughout life, but its regulation is still poorly understood. One NSC can give birth to two NSCs or one NSC and one transient progenitor. A correct balance is necessary for the maintenance of germinal areas, and understanding the molecular mechanisms underlying NSC division mode is clearly important. Here, we report a function of the Sonic Hedgehog (SHH) receptor Patched in the direct control of long-term NSC self-renewal in the subependymal zone. We show that genetic conditional activation of SHH signaling in adult NSCs leads to their expansion and the depletion of their direct progeny. These phenotypes are associated in vitro with an increase in NSC symmetric division in a process involving NOTCH signaling. Together, our results demonstrate a tight control of adult neurogenesis and NSC renewal driven by Patched.
authors.affiliation: Laboratory of Neurobiology and Development-CNRS, Signal Transduction and Developmental Neuropharmacology Team, Institute of Neurobiology Alfred Fessard, Gif-sur-Yvette 91198, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Ferent
authors.affiliation: Laboratory of Neurobiology and Development-CNRS, Signal Transduction and Developmental Neuropharmacology Team, Institute of Neurobiology Alfred Fessard, Gif-sur-Yvette 91198, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Cochard
authors.affiliation: Laboratory of Neurobiology and Development-CNRS, Signal Transduction and Developmental Neuropharmacology Team, Institute of Neurobiology Alfred Fessard, Gif-sur-Yvette 91198, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Faure
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, 53100 Siena, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Taddei
authors.affiliation: Tumor Genetics Group, Institute of Human Genetics, University Medical Center, Göttingen 37073, Germany.
authors.forename: Heidi
authors.initials: H
authors.lastname: Hahn
authors.affiliation: Laboratory of Neurobiology and Development-CNRS, Signal Transduction and Developmental Neuropharmacology Team, Institute of Neurobiology Alfred Fessard, Gif-sur-Yvette 91198, France. Electronic address: ruat@inaf.cnrs-gif.fr.
authors.forename: Martial
authors.initials: M
authors.lastname: Ruat
authors.affiliation: Laboratory of Neurobiology and Development-CNRS, Signal Transduction and Developmental Neuropharmacology Team, Institute of Neurobiology Alfred Fessard, Gif-sur-Yvette 91198, France. Electronic address: elisabeth.traiffort@inserm.fr.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Traiffort
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis; D000072079:Patched Receptors; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology; D015398:Signal Transduction; D013629:Tamoxifen / Q000494:pharmacology; D015854:Up-Regulation; D000071676:Zinc Finger Protein GLI1
chemical_list: D027322:Amino Acid Transport System X-AG; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; D020845:Selective Estrogen Receptor Modulators; D000071676:Zinc Finger Protein GLI1; D013629:Tamoxifen