title: Suppressor of Fused Is Critical for Maintenance of Neuronal Progenitor Identity during Corticogenesis.
abstract: Proper lineage progression and diversification of neural progenitor cells (NPCs) ensures the generation of projection neuron (PN) subtypes in the mammalian neocortex. Here, we show that Suppressor of Fused (Sufu) controls PN specification by maintaining the identity of NPCs in the embryonic neocortex. Deletion of Sufu in NPCs of the E10.5 mouse neocortex led to improper specification of progenitors and a reduction in intermediate progenitors (IPs) during corticogenesis. We found that Sufu deletion resulted in unstable Gli2 and Gli3 activity, leading to the ectopic activation of Sonic hedgehog (Shh) signaling. The role of Sufu in maintaining progenitor identity is critical at early stages of corticogenesis, since deletion of Sufu at E13.5 did not cause similar abnormalities. Our studies revealed that Sufu critically modulates Shh signaling at early stages of neurogenesis for proper specification and maintenance of cortical NPCs to ensure the appropriate generation of cortical PN lineages.
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Odessa R
authors.initials: OR
authors.lastname: Yabut
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Fernandez
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Trung
authors.initials: T
authors.lastname: Huynh
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA; College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do 16419, Republic of Korea.
authors.forename: Keejung
authors.initials: K
authors.lastname: Yoon
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA; Programs in Neuroscience and Developmental Biology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: sam.pleasure@ucsf.edu.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Pleasure
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004622:Embryo, Mammalian; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D019579:Neocortex / Q000196:embryology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics*; D015398:Signal Transduction; D013997:Time Factors; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
chemical_list: C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; C465570:Shh protein, mouse; C490763:Sufu protein, mouse; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3