title: The Dorsoventral Patterning of Human Forebrain Follows an Activation/Transformation Model.
abstract: The anteroposterior patterning of the central nervous system follows an activation/transformation model, which proposes that a prospective telencephalic fate will be activated by default during the neural induction stage, while this anterior fate could be transformed posteriorly according to caudalization morphogens. Although both extrinsic signals and intrinsic transcription factors have been implicated in dorsoventral (DV) specification of vertebrate telencephalon, the DV patterning model remains elusive. This is especially true in human considering its evolutionary trait and uniqueness of gene regulatory networks during neural induction. Here, we point to a model that human forebrain DV patterning also follows an activation/transformation paradigm. Human neuroectoderm (NE) will activate a forebrain dorsal fate automatically and this default anterior dorsal fate does not depend on Wnts activation or Pax6 expression. Forced expression of Pax6 in human NE hinders its ventralization even under sonic hedgehog (Shh) treatment, suggesting that the ventral fate is repressed by dorsal genes. Genetic manipulation of Nkx2.1, a key gene for forebrain ventral progenitors, shows that Nkx2.1 is neither necessary nor sufficient for Shh-driven ventralization. We thus propose that Shh represses dorsal genes of human NE and subsequently transforms the primitively activated dorsal fate ventrally in a repression release manner.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences and.|School of Life Sciences, Zhengzhou University, Zhengzhou, Henan Province 450001, China.|Shanghai Tenth People's Hospital, and Neuroregeneration Key Laboratory of Shanghai Universities, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Liankai
authors.initials: L
authors.lastname: Chi
authors.affiliation: Shanghai Tenth People's Hospital, and Neuroregeneration Key Laboratory of Shanghai Universities, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Fan
authors.affiliation: Shanghai Tenth People's Hospital, and Neuroregeneration Key Laboratory of Shanghai Universities, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Feng
authors.affiliation: Shanghai Tenth People's Hospital, and Neuroregeneration Key Laboratory of Shanghai Universities, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Shanghai Tenth People's Hospital, and Neuroregeneration Key Laboratory of Shanghai Universities, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Anatomy and Neurobiology, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Jiangsu 226001, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Hui
authors.affiliation: Shanghai Tenth People's Hospital, and Neuroregeneration Key Laboratory of Shanghai Universities, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Xiangjie
authors.initials: X
authors.lastname: Xu
authors.affiliation: Shanghai Tenth People's Hospital, and Neuroregeneration Key Laboratory of Shanghai Universities, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ma
authors.affiliation: Shanghai Tenth People's Hospital, and Neuroregeneration Key Laboratory of Shanghai Universities, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Yujiang
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Shanghai Tenth People's Hospital, and Neuroregeneration Key Laboratory of Shanghai Universities, Tongji University School of Medicine, Shanghai 200092, China.
authors.forename: Quanbin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Anatomy and Neurobiology, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Jiangsu 226001, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Jin
authors.affiliation: Shanghai Tenth People's Hospital, and Neuroregeneration Key Laboratory of Shanghai Universities, Tongji University School of Medicine, Shanghai 200092, China.|Advanced Institute of Translational Medicine.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Zhengzhou University, Zhengzhou, Henan Province 450001, China.
authors.forename: Fangxia
authors.initials: F
authors.lastname: Guan
authors.affiliation: Shanghai Tenth People's Hospital, and Neuroregeneration Key Laboratory of Shanghai Universities, Tongji University School of Medicine, Shanghai 200092, China.|Advanced Institute of Translational Medicine.|The Collaborative Innovation Center for Brain Science, Tongji University, Shanghai 200092, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Zhang
mesh_terms: D019521:Body Patterning / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D053595:Embryonic Stem Cells; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors; D014162:Transfection
chemical_list: D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger
keywords: Wnts; brain development; human embryonic stem cells; neural differentiation; regional patterning; sonic hedgehog