title: Wnt7a regulates multiple steps of neurogenesis.
abstract: Although Wnt7a has been implicated in axon guidance and synapse formation, investigations of its role in the early steps of neurogenesis have just begun. We show here that Wnt7a is essential for neural stem cell self-renewal and neural progenitor cell cycle progression in adult mouse brains. Loss of Wnt7a expression dramatically reduced the neural stem cell population and increased the rate of cell cycle exit in neural progenitors in the hippocampal dentate gyrus of adult mice. Furthermore, Wnt7a is important for neuronal differentiation and maturation. Loss of Wnt7a expression led to a substantial decrease in the number of newborn neurons in the hippocampal dentate gyrus. Wnt7a(-/-) dentate granule neurons exhibited dramatically impaired dendritic development. Moreover, Wnt7a activated β-catenin and its downstream target genes to regulate neural stem cell proliferation and differentiation. Wnt7a stimulated neural stem cell proliferation by activating the β-catenin-cyclin D1 pathway and promoted neuronal differentiation and maturation by inducing the β-catenin-neurogenin 2 pathway. Thus, Wnt7a exercised critical control over multiple steps of neurogenesis by regulating genes involved in both cell cycle control and neuronal differentiation.
authors: Department of Neurosciences, Beckman Research Institute of City of Hope, Duarte, California, USA.
authors: Qiuhao
authors: Q
authors: Qu
authors: Guoqiang
authors: G
authors: Sun
authors: Kiyohito
authors: K
authors: Murai
authors: Peng
authors: P
authors: Ye
authors: Wendong
authors: W
authors: Li
authors: Grace
authors: G
authors: Asuelime
authors: Yuen-Ting
authors: YT
authors: Cheung
authors: Yanhong
authors: Y
authors: Shi
mesh_terms: D000367:Age Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D016548:Prosencephalon / Q000166:cytology / Q000254:growth & development; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019938:Cyclin D1; D009419:Nerve Tissue Proteins; D051153:Wnt Proteins; D051176:beta Catenin; C530105:Ccnd1 protein, mouse; C102938:Neurog2 protein, mouse; C490508:Wnt7a protein, mouse
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