title: A genome-wide screen for spatially restricted expression patterns identifies transcription factors that regulate glial development.
abstract: Forward genetic screens in genetically accessible invertebrate organisms such as Drosophila melanogaster have shed light on transcription factors that specify formation of neurons in the vertebrate CNS. However, invertebrate models have, to date, been uninformative with respect to genes that specify formation of the vertebrate glial lineages. All recent insights into specification of vertebrate glia have come via monitoring the spatial and temporal expression patterns of individual transcription factors during development. In studies described here, we have taken this approach to the genome scale with an in silico screen of the Mahoney pictorial atlas of transcription factor expression in the developing CNS. From the population of 1445 known or probable transcription factors encoded in the mouse genome, we identify 12 novel transcription factors that are expressed in glial lineage progenitor cells. Entry-level screens for biological function establish one of these transcription factors, Klf15, as sufficient for genesis of precocious GFAP-positive astrocytes in spinal cord explants. Another transcription factor, Tcf4, plays an important role in maturation of oligodendrocyte progenitors.
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, and Departments of Neurobiology and Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Fu
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.forename: Eva
authors.initials: E
authors.lastname: Fast
authors.forename: Susan
authors.initials: S
authors.lastname: Gray
authors.forename: Rachel
authors.initials: R
authors.lastname: Greenberg
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Jain
authors.forename: Qiufu
authors.initials: Q
authors.lastname: Ma
authors.forename: Mengsheng
authors.initials: M
authors.lastname: Qiu
authors.forename: David H
authors.initials: DH
authors.lastname: Rowitch
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Taylor
authors.forename: Charles D
authors.initials: CD
authors.lastname: Stiles
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005820:Genetic Testing / Q000379:methods; D016678:Genome / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000166:cytology / Q000502:physiology*; D011247:Pregnancy; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D014157:Transcription Factors