title: Caspr Controls the Temporal Specification of Neural Progenitor Cells through Notch Signaling in the Developing Mouse Cerebral Cortex.
abstract: The generation of layer-specific neurons and astrocytes by radial glial cells during development of the cerebral cortex follows a precise temporal sequence, which is regulated by intrinsic and extrinsic factors. The molecular mechanisms controlling the timely generation of layer-specific neurons and astrocytes remain not fully understood. In this study, we show that the adhesion molecule contactin-associated protein (Caspr), which is involved in the maintenance of the polarized domains of myelinated axons, is essential for the timing of generation of neurons and astrocytes in the developing mouse cerebral cortex. Caspr is expressed by radial glial cells, which are neural progenitor cells that generate both neurons and astrocytes. Absence of Caspr in neural progenitor cells delays the production cortical neurons and induces precocious formation of cortical astrocytes, without affecting the numbers of progenitor cells. At the molecular level, Caspr cooperates with the intracellular domain of Notch to repress transcription of the Notch effector Hes1. Suppression of Notch signaling via a Hes1 shRNA rescues the abnormal neurogenesis and astrogenesis in Caspr-deficient mice. These findings establish Caspr as a novel key regulator that controls the temporal specification of cell fate in radial glial cells of the developing cerebral cortex through Notch signaling.
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Second Affiliated Hospital, Soochow University, Suzhou, Jiangsu Province 215123, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Second Affiliated Hospital, Soochow University, Suzhou, Jiangsu Province 215123, China.
authors.forename: Di
authors.initials: D
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Second Affiliated Hospital, Soochow University, Suzhou, Jiangsu Province 215123, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Forensic Medicine, Soochow University, Suzhou, Jiangsu Province 215123, China.
authors.forename: Xi-Ping
authors.initials: XP
authors.lastname: Chen
authors.affiliation: Department of Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, Homburg D-66421, Germany.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Huang
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Second Affiliated Hospital, Soochow University, Suzhou, Jiangsu Province 215123, China.
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Second Affiliated Hospital, Soochow University, Suzhou, Jiangsu Province 215123, China.
authors.forename: He-Qing
authors.initials: HQ
authors.lastname: Zhao
authors.affiliation: Affiliated Bayi Brain Hospital, Beijing Military Hospital, Southern Medical University, Beijing 100070, China.
authors.forename: Ru-Xiang
authors.initials: RX
authors.lastname: Xu
authors.affiliation: Binzhou Medical University, Yantai, Shandong Province 264000, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong Province 515041, China.
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
authors.affiliation: Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Second Affiliated Hospital, Soochow University, Suzhou, Jiangsu Province 215123, China.
authors.forename: Quan-Hong
authors.initials: QH
authors.lastname: Ma
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002454:Cell Differentiation / Q000502:physiology; D002540:Cerebral Cortex / Q000254:growth & development*; D063928:Ependymoglial Cells / Q000378:metabolism; D018345:Mice, Knockout; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse; D051880:Receptors, Notch
keywords: brain development; cntnap1; gliogenesis; neurogenesis; radial glia