title: Control of astrocyte progenitor specification, migration and maturation by Nkx6.1 homeodomain transcription factor.
abstract: Although astrocytes are the most abundant cell type in the central nervous system (CNS), little is known about their molecular specification and differentiation. It has previously been reported that transcription factor Nkx6.1 is expressed in neuroepithelial cells that give rise to astrocyte precursors in the ventral spinal cord. In the present study, we systematically investigated the function of Nkx6.1 in astrocyte development using both conventional and conditional Nkx6.1 mutant mice. At early postnatal stages, Nkx6.1 was expressed in a subpopulation of astrocytes in the ventral spinal cord. In the conventional Nkx6.1KO spinal cord, the initial specification of astrocyte progenitors was affected by the mutation, and subsequent migration and differentiation were disrupted in newborn mice. In addition, the development of VA2 subtype astrocytes was also inhibited in the white matter. Further studies with Nkx6.1 conditional mutants revealed significantly delayed differentiation and disorganized arrangement of fibrous astrocytes in the ventral white matter. Together, our studies indicate that Nkx6.1 plays a vital role in astrocyte specification and differentiation in the ventral spinal cord.
authors.affiliation: Institute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China; Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Institute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China.
authors.forename: Yidan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Institute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
authors.affiliation: Institute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Teng
authors.affiliation: Institute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Zheng
authors.affiliation: Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Hu
authors.affiliation: Institute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China.
authors.forename: Binghua
authors.initials: B
authors.lastname: Xie
authors.affiliation: Institute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China.
authors.forename: Zunyi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Departments of Pediatrics and Cellular and Molecular Medicine, Pediatric Diabetes Research Center, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Maike
authors.initials: M
authors.lastname: Sander
authors.affiliation: Institute of Developmental and Regenerative Biology, Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China; Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Mengsheng
authors.initials: M
authors.lastname: Qiu
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D066128:Gray Matter / Q000166:cytology; D018398:Homeodomain Proteins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D066127:White Matter / Q000166:cytology
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C491328:Nkx6-1 protein, mouse; C491327:Nkx6-1 protein, rat; D064568:S100 Calcium Binding Protein beta Subunit; C120010:Slit1 protein, mouse