A genome-wide screen for spatially restricted expression patterns identifies transcription factors that regulate glial development

TY - JOUR

T1 - A genome-wide screen for spatially restricted expression patterns identifies transcription factors that regulate glial development

AU - Fu, H.

AU - Cai, J.

AU - Clevers, H.

AU - Fast, E.

AU - Gray, S.

AU - Greenberg, R.

AU - Jain, M.K.

AU - Ma, Q.

AU - Qiu, M.

AU - Rowitch, D.H.

AU - Taylor, C.

AU - Stiles, C.D.

N1 - Reporting year: 2009 Metis note: 29/36/11399

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1523/JNEUROSCI.0160-09.2009

DO - 10.1523/JNEUROSCI.0160-09.2009

M3 - Article

SN - 0270-6474

VL - 29

SP - 11399

EP - 11408

JO - Journal of Neuroscience

JF - Journal of Neuroscience

IS - 36

ER -