Sox1 acts through multiple independent pathways to promote neurogenesis.
Although Sox1, Sox2, and Sox3 are all part of the Sox-B1 group of transcriptional regulators, only Sox1 appears to play a direct role in neural cell fate determination and differentiation. We find that overexpression of Sox1 but not Sox2 or Sox3 in cultured neural progenitor cells is sufficient to induce neuronal lineage commitment. Sox1 binds directly to the Hes1 promoter and suppresses Hes1 transcription, thus attenuating Notch signaling. Sox1 also binds to beta-catenin and suppresses beta-catenin-mediated TCF/LEF signaling, thus potentially attenuating the wnt signaling pathway. The C-terminus of Sox1 is required for both of these interactions. Sox1 also promotes exit of cells from cell cycle and up-regulates transcription of the proneural bHLH transcription factor neurogenin 1 (ngn1). These observations suggest that Sox1 works through multiple independent pathways to promote neuronal cell fate determination and differentiation.
Kan
Lixin
L
Department of Neurology, Northwestern University's Feinberg School of Medicine, Chicago, IL 60611-3008, USA. 1-kan@northwestern.edu
Israsena
Nipan
N
Zhang
Zuoli
Z
Hu
Min
M
Zhao
Li-Ru
LR
Jalali
Ali
A
Sahni
Vibhu
V
Kessler
John A
JA
D051792:Basic Helix-Loop-Helix Proteins; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D006609:High Mobility Group Proteins / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000502:physiology*; D011401:Promoter Regions, Genetic; D055748:SOXB1 Transcription Factors; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000235:genetics; D051176:beta Catenin
D051792:Basic Helix-Loop-Helix Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D055748:SOXB1 Transcription Factors; D015534:Trans-Activators; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; D051176:beta Catenin; C495270:CTNNB1 protein, human; C489734:Hes1 protein, mouse; C105389:NEUROG1 protein, human; C490906:SOX1 protein, human; C527785:SOX3 protein, human; C527786:Sox3 protein, mouse; C078493:HES1 protein, human; C486336:Neurog1 protein, mouse