Endogenous Neuregulin Restores Radial Glia in a (Ferret) Model of Cortical Dysplasia

Gierdalski, Marcin; Sardi, S. Pablo; Corfas, Gabriel; Juliano, Sharon L.

doi:10.1523/jneurosci.1476-05.2005

Cited by 22 publications

(27 citation statements)

References 47 publications

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“…Moreover, exogenous application of NRG1 restores radial glial morphology in E24 MAM-treated cortex and acts via ErbB3 and ErbB4 receptor signaling (Gierdalski et al, 2005). In the current study we restore the migration pattern of cells leaving the GE by rescuing radial glia morphology.…”

Section: Ngr1 Restores Tangential Migrationmentioning

confidence: 48%

“…We recently demonstrated that neuregulin (NRG1) added to the media of E24 MAM-treated cultures restores the elongated morphology of radial glial cells (Gierdalski et al, 2005). To determine if restored radial glia morphology improves the ability of tangentially migrating cells to reach the CP, we added NRG1 to the media of normal and E24 MAM-treated organotypic cultures and injected DiI into the GE.…”

Section: Normal Rg Morphology Is Necessary For the Proper Positioningmentioning

confidence: 99%

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A normal radial glial scaffold is necessary for migration of interneurons during neocortical development

Poluch

Juliano

2007

Glia

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The relationship between radial glia and neurons migrating tangentially from the ganglionic eminence (GE) has been suggested but not firmly established. To study this relationship we used a ferret model of cortical dysplasia where radial glia are highly disorganized. To produce this, an antimitotic, methylazoxy methanol (MAM) is injected on the 24th day of gestation (E24 MAM). Neurons migrating away from the GE in MAM-treated animals tend to remain in the intermediate zone (IZ) and do not reach the cortical plate (CP) as they do in normal ferret slices. We recently observed that the disrupted radial glia after MAM treatment could be restored toward their normal morphology by exogenous application of neuregulin1 (NRG1). We demonstrate here that when E24 MAM slices are treated with NRG1, the distribution of cells arising from the GE was similar to normal slices. In a second paradigm, we disrupted radial glia by adding ciliary neurotrophic factor (CNTF) to the culture media of normal ferret slices; CNTF induces acute differentiation of radial glia into astrocytes. After CNTF exposure, few tangentially migrating cells reach the CP compared to untreated slices. These results show that interneurons fail to reach the CP by disrupted normal radial glia and restoring the normal radial glial scaffold is sufficient to allow migrating cells to invade the CP. Our results suggest an important role for radial glia by controlling directly or indirectly the migration of interneurons to the CP, their main target.

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Section: Ngr1 Restores Tangential Migrationmentioning

confidence: 48%

Section: Normal Rg Morphology Is Necessary For the Proper Positioningmentioning

confidence: 99%

A normal radial glial scaffold is necessary for migration of interneurons during neocortical development

Poluch

Juliano

2007

Glia

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“…Radial glia maintenance and/or differentiation results from a balance between neurogenic and stem cell-maintaining molecules such as neuregulin-1 and Notch1 [14,15,16,17,73,74,75,76,77,78,79], and differentiating molecules such as TGF-β 1 [26,80], cardiotrophin [25] and ciliary neurotrophic factor [18], which are crucial to control the correct timing of the neurogenic-to-gliogenic switch of radial glia cells. …”

Section: Discussionmentioning

confidence: 99%

Activation of MAPK/PI3K/SMAD Pathways by TGF-β1 Controls Differentiation of Radial Glia into Astrocytes in vitro

Stipursky

Francis

Gomes³

2012

Dev Neurosci

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The major neural stem cell population in the developing cerebral cortex is the radial glia cells, which generate neurons and glial cells. The mechanisms that modulate the maintenance of the radial glia stem cell phenotype, or its differentiation, are not completely elucidated. We previously demonstrated that transforming growth factor-β₁ (TGF-β₁) promotes radial glia differentiation into astrocytes in vitro [Glia 2007;55:1023–1033]. Here we investigated the intracellular signaling pathways involved in the TGF-β₁-induced radial glia fate commitment. We demonstrate that the mechanisms underlying the TGF-β₁ effect on radial glia cell differentiation or progenitor potential maintenance diverge. Whereas radial glia differentiation into astrocytes is mediated by the activation of the MAPK signaling pathway, neurogenesis is modulated by different levels of PI3K and SMAD2/3 activity. Our work demonstrates that radial glia cells are a heterogeneous population and a potential target of TGF-β₁, and suggests that its effect on radial glia fate commitment is mediated by the recruitment of a complex multipathway mechanism that controls astrocyte and neuronal generation in the developing cerebral cortex.

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“…Interestingly, a recent study showed that treatment of MAMexposed slices with neuregulin was sufficient to rescue radial glial defects but not Cajal-Retzius cell positioning defects (Gierdalski et al, 2005). This suggested that marginal zone defects after MAM exposure are reversible and that a teratogenic insult might cause marginal zone dysplasia by affecting only a small number of molecular pathways.…”

Section: Disruption Of the Marginal Zone After Mam Exposurementioning

confidence: 99%

Stromal-Derived Factor-1 (CXCL12) Regulates Laminar Position of Cajal-Retzius Cells in Normal and Dysplastic Brains

Paredes

Li²,

Berger³

et al. 2006

J. Neurosci.

119

111

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Normal brain development requires a series of highly complex and interrelated steps. This process presents many opportunities for errors to occur, which could result in developmental defects in the brain, clinically referred to as malformations of cortical development. The marginal zone and Cajal-Retzius cells are key players in cortical development and are established early, yet there is little understanding of the factors resulting in the disruption of the marginal zone in many types of cortical malformation syndromes. We showed previously that treatment with methylazoxymethanol in rats causes marginal zone dysplasia with displacement of Cajal-Retzius cells to deeper cortical layers. Here we establish that loss of activity of the chemokine stromal-derived factor-1 (SDF1) (CXCL12), which is expressed by the leptomeninges, is necessary and sufficient to cause marginal zone disorganization in this widely used teratogenic animal model. We also found that mice with mutations in the main receptor for SDF1 (CXCR4) have Cajal-Retzius cells displaced to deeper cortical layers. Furthermore, by inhibiting SDF1 signaling in utero by intraventricular injection of a receptor antagonist, we establish that SDF1 signaling is required for the maintenance of Cajal-Retzius cell position in the marginal zone during normal cortical development. Our data imply that cortical layering is not a static process, but rather requires input from locally produced molecular cues for maintenance, and that complex syndromes of cortical malformation as a result of environmental insults may still be amenable to explanation by interruption of specific molecular signaling pathways.

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Endogenous Neuregulin Restores Radial Glia in a (Ferret) Model of Cortical Dysplasia

Cited by 22 publications

References 47 publications

A normal radial glial scaffold is necessary for migration of interneurons during neocortical development

A normal radial glial scaffold is necessary for migration of interneurons during neocortical development

Activation of MAPK/PI3K/SMAD Pathways by TGF-β1 Controls Differentiation of Radial Glia into Astrocytes in vitro

Stromal-Derived Factor-1 (CXCL12) Regulates Laminar Position of Cajal-Retzius Cells in Normal and Dysplastic Brains

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