Midline radial glia translocation and corpus callosum formation require FGF signaling

Smith, Karen; Ohkubo, Yasushi; Maragnoli, Maria Elisabetta; Rašin, Mladen-Roko; Schwartz, Michael L.; Šestan, Nenad; Vaccarino, Flora M.

doi:10.1038/nn1705

Cited by 138 publications

(162 citation statements)

References 50 publications

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“…Further support for this idea comes from the analysis of Hs6st1 Ϫ/Ϫ ; Slit2 Ϫ/Ϫ embryos which provide clear evidence for nonepistatic relations between Slit2 and Hs6st1. The absence of glia in the IG and the ectopically located glia that we find in Hs6st1 Ϫ/Ϫ embryos, neither of which is seen in Robo/Slit mutants (Bagri et al, 2002;Andrews et al, 2006), resemble the phenotype reported in conditional FGFR1 Ϫ/Ϫ mutant embryos, which have reduced levels of FGF signaling (Smith et al, 2006;Tole et al, 2006;Moldrich et al, 2010) (compare phenotype summaries in Fig. 11 K and M, N ).…”

Section: Slit1supporting

confidence: 72%

“…11 K and M, N ). The normal differentiation and migration of glia which form the GW and IG starts at E14.5 and requires FGF signaling (Smith et al, 2006;Tole et al, 2006). To determine whether reduced FGF signaling could contribute to the Hs6st1 Ϫ/Ϫ callosal phenotype we examined the expression of Sprouty2, a transcriptional target of FGF signaling, at the telencephalic midline.…”

Section: Slit1mentioning

confidence: 99%

“…Corpus callosum development is a complex event requiring the precise coordination of tissue fusion, neuron and glial cell production, cell migration, and axon guidance molecule expression (Serafini et al, 1996;Bagri et al, 2002;Shu et al, 2003a,b;Andrews et al, 2006;Keeble et al, 2006;Smith et al, 2006;Tole et al, 2006;Lindwall et al, 2007;Ló pez-Bendito et al, 2007;Paul et al, 2007;Islam et al, 2009;Niquille et al, 2009). Embryos lacking the HS biosynthetic enzyme Ext1 in the developing CNS exhibit severe morphological distortions at the telencephalic midline and axons fail to connect the cerebral hemispheres illustrating the vital importance of HS in this developing system (Inatani et al, 2003).…”

Section: The Corpus Callosummentioning

confidence: 99%

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Heparan Sulfate Sugar Modifications Mediate the Functions ofSlitsand Other Factors Needed for Mouse Forebrain Commissure Development

Conway¹,

Howe²,

Nettleton³

et al. 2011

J. Neurosci.

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Heparan sulfate proteoglycans are cell surface and secretory proteins that modulate intercellular signaling pathways including Slit/Robo and FGF/FGFR. The heparan sulfate sugar moieties on HSPGs are subject to extensive postsynthetic modification, generating enormous molecular complexity that has been postulated to provide increased diversity in the ability of individual cells to respond to specific signaling molecules. This diversity could help explain how a relatively small number of axon guidance molecules are able to instruct the extremely complex connectivity of the mammalian brain. Consistent with this hypothesis, we previously showed that mutant mice lacking the heparan sulfotransferases (Hsts) Hs2st or Hs6st1 display major axon guidance defects at the developing optic chiasm. Here we further explore the role of these Hsts at the optic chiasm and investigate their function in corpus callosum development. Each Hst is expressed in a distinct pattern and each mutant displays a specific spectrum of axon guidance defects. Particular Hs2st ؊/؊ and Hs6st1phenotypes closely match those of Slit1 ؊/؊ and Slit2 ؊/؊ embryos respectively, suggesting possible functional relationships. To test functional interactions between Hs2st or Hs6st1 and Slits we examined optic chiasm and corpus callosum phenotypes in a panel of genotypes where Hs2st or Hs6st1 and Slit1 or Slit2 function were simultaneously reduced or absent. We find examples of Hs2st and Hs6st1 having epistatic, synergistic, and antagonistic genetic relationships with Slit1 and/or Slit2 depending on the context. At the corpus callosum we find that Hs6st1 has Slit-independent functions and our data indicate additional roles in FGF signaling.

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Section: Slit1supporting

confidence: 72%

Section: Slit1mentioning

confidence: 99%

Section: The Corpus Callosummentioning

confidence: 99%

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Heparan Sulfate Sugar Modifications Mediate the Functions ofSlitsand Other Factors Needed for Mouse Forebrain Commissure Development

Conway¹,

Howe²,

Nettleton³

et al. 2011

J. Neurosci.

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show abstract

“…Also, exogenous application of Fgf9 induces proliferation of Fgfr2/3-positive Müller glial cells in vitro 42 . In the neocortex, analysis of both Fgfr2 and Gfap conditional knockouts and Fgfr1/Fgfr2 and Gfap double mutants showed a decrease in the density of astrocytes in the dorsal neocortex 43 .…”

Section: Discussionmentioning

confidence: 99%

Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors

et al. 2009

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The fate of cortical progenitors, which progressively generate neurons and glial cells during development, is determined by temporally and spatially regulated signaling mechanisms. We found that the transcription factor Sip1 (Zfhx1b), which is produced at high levels in postmitotic neocortical neurons, regulates progenitor fate non-cell autonomously. Conditional deletion of Sip1 in young neurons induced premature production of upper-layer neurons at the expense of deep layers, precocious and increased generation of glial precursors, and enhanced postnatal astrocytogenesis. The premature upper-layer generation coincided with overexpression of the neurotrophin-3 (Ntf3) gene and upregulation of fibroblast growth factor 9 (Fgf9) gene expression preceded precocious gliogenesis. Exogenous application of Fgf9 to mouse cortical slices induced excessive generation of glial precursors in the germinal zone. Our data suggest that Sip1 restrains the production of signaling factors in postmitotic neurons that feed back to progenitors to regulate the timing of cell fate switch and the number of neurons and glial cells throughout corticogenesis.

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“…These embryonic multipotent progenitors, also called "radial glia," span the entire cortical wall and generate through asymmetric cell divisions neural precursors that eventually differentiate into neurons and migrate to the cerebral cortex (Noctor et al, 2001;Englund et al, 2005;Gal et al, 2006). After the completion of cortical neurogenesis, radial glia transform into astrocytes by retracting their apical (ventricular) processes and migrating upward toward the cortical plate (Schmechel and Rakic, 1979;Pixley and de Vellis, 1984;Smith et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Early Postnatal Astroglial Cells Produce Multilineage Precursors and Neural Stem CellsIn Vivo

et al. 2006

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To identify the fates that astroglial cells can attain in the postnatal brain, we generated mice carrying an inducible Cre recombinase (Cre-ER T2 ) controlled by the human GFAP promoter (hGFAP). In mice carrying the GCE (hGFAP-Cre-ER T2 ) transgene, OHT (4-hydroxytamoxifen) injections induced Cre recombination in astroglial cells at postnatal day 5 and allowed us to permanently tag these cells with reporter genes. Three days after recombination, reporter-tagged cells were quiescent astroglial cells that expressed the stem cell marker LeX in the subventricular zone (SVZ) and dentate gyrus (DG). After 2-4 weeks, the tagged GFAP lineage included proliferating progenitors expressing the neuronal marker Dcx (Doublecortin) in the SVZ and the DG. After 4 weeks, the GFAP lineage generated mature neurons in the olfactory bulb (OB), DG, and, strikingly, also in the cerebral cortex. A major portion of all neurons in the DG and OB born at the end of the first postnatal week were generated from GFAP ϩ cells. In addition to neurons, mature oligodendrocytes and astrocytes populating the cerebral cortex and white matter were also the progeny of GFAP ϩ astroglial ancestors. Thus, genetic fate mapping of postnatal GFAP ϩ cells reveals that they seed the postnatal brain with neural progenitors/stem cells that in turn give rise to neural precursors and their mature neuronal and oligodendrocytic progeny in many CNS regions, including the cerebral cortex.

show abstract

Midline radial glia translocation and corpus callosum formation require FGF signaling

Cited by 138 publications

References 50 publications

Heparan Sulfate Sugar Modifications Mediate the Functions ofSlitsand Other Factors Needed for Mouse Forebrain Commissure Development

Heparan Sulfate Sugar Modifications Mediate the Functions ofSlitsand Other Factors Needed for Mouse Forebrain Commissure Development

Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors

Early Postnatal Astroglial Cells Produce Multilineage Precursors and Neural Stem CellsIn Vivo

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