Reinduction of ErbB2 in astrocytes promotes radial glial progenitor identity in adult cerebral cortex

Ghashghaei, H. Troy; Weimer, Jill M.; Schmid, Ralf S.; Yokota, Yukako; McCarthy, Ken D.; Popko, Brian; Anton, E. S.

doi:10.1101/gad.1580407

Cited by 63 publications

(49 citation statements)

References 86 publications

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“…60,61 Other groups demonstrated that mature astrocytes locally resume proliferation and dedifferentiate in response to brain injury and other stimuli. 57,62 Thus, both scenarios can occur. In our study, nestin-positive reactive astrocytes were observed very early during cancer cell invasion of the brain parenchyma.…”

Section: Discussionmentioning

confidence: 99%

Capturing Changes in the Brain Microenvironment during Initial Steps of Breast Cancer Brain Metastasis

Lorger

Felding-Habermann

2010

The American Journal of Pathology

287

302

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Brain metastases are diagnosed in 10 to 40% of all cancer patients, and the incidence is rising as patients live longer due to improved treatments for extracranial metastases.1,2 Brain lesions are most frequently associated with lung cancer, breast cancer, and melanoma. 1,2 Unfortunately, brain metastases are still very difficult to treat and the mechanisms underlying their establishment and progression are poorly understood. Thus, information in this direction and models for analysis are a prerequisite for the development of new, efficient therapies.The essential role of the tumor microenvironment in cancer progression has been well documented for extracranial malignancies, and recent findings indicate that the tumor microenvironment might be a suitable target in anticancer therapies, as well as a valuable biomarker for prognostic purposes.3-5 The brain provides a unique environment with paracrine growth factors that differ from most other organs. 6,7 The involvement of brain-resident cells including brain endothelial cells, microglia, and astrocytes in the pathology of primary and metastatic brain tumors is only partially understood. Brain endothelial cells are the first host cell type that circulating cancer cells encounter when they arrest within the brain microvasculature. In addition to posing the initial barrier for brain invasion, endothelial cells and their basement membrane seem to play important roles in supporting the growth of brain metastases as well as brain tumor stem cells. 8 -10

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Section: Discussionmentioning

confidence: 99%

Capturing Changes in the Brain Microenvironment during Initial Steps of Breast Cancer Brain Metastasis

Lorger

Felding-Habermann

2010

The American Journal of Pathology

287

302

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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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“…For cell transplantation studies, FoxJ1 -/-EGFP or FoxJ1 +/+EGFP cells were injected into the lateral ventricles of wild-type and FoxJ1-null animals using a stereotaxic apparatus. Cell preparations were obtained using fluorescence-activated cell sorting (Dako Cytomation MoFlo; NCSU Flow Cytometry and Cell Sorting Laboratory), followed by resuspension in artificial cerebrospinal fluid (Ghashghaei et al, 2007b) supplemented with 10 ng of epidermal growth factor (Egf) and fibroblast growth factor (Fgf2) to a final concentration of 1 ϫ 10 6 EGFP + cells/l. For both transplantation and lentiviral injections, newborn pups (P0) were anesthetized by means of hypothermia as described previously (Ghashghaei et al, 2007b).…”

Section: Intraventricular Lentiviral and Cell Injectionsmentioning

confidence: 99%

“…Cell preparations were obtained using fluorescence-activated cell sorting (Dako Cytomation MoFlo; NCSU Flow Cytometry and Cell Sorting Laboratory), followed by resuspension in artificial cerebrospinal fluid (Ghashghaei et al, 2007b) supplemented with 10 ng of epidermal growth factor (Egf) and fibroblast growth factor (Fgf2) to a final concentration of 1 ϫ 10 6 EGFP + cells/l. For both transplantation and lentiviral injections, newborn pups (P0) were anesthetized by means of hypothermia as described previously (Ghashghaei et al, 2007b). For shFoxJ1-lenti and control-lenti vector injections, 1 l of each vector (10 10 infectious units/ml) was injected into the anterior lateral ventricles of P0 pups using stereotaxic surgery (n3 per construct …”

Section: Intraventricular Lentiviral and Cell Injectionsmentioning

confidence: 99%

FoxJ1-dependent gene expression is required for differentiation of radial glia into ependymal cells and a subset of astrocytes in the postnatal brain

et al. 2009

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Neuronal specification occurs at the periventricular surface of the embryonic central nervous system. During early postnatal periods, radial glial cells in various ventricular zones of the brain differentiate into ependymal cells and astrocytes. However, mechanisms that drive this time-and cell-specific differentiation remain largely unknown. Here, we show that expression of the forkhead transcription factor FoxJ1 in mice is required for differentiation into ependymal cells and a small subset of FoxJ1 + astrocytes in the lateral ventricles, where these cells form a postnatal neural stem cell niche. Moreover, we show that a subset of FoxJ1 + cells harvested from the stem cell niche can self-renew and possess neurogenic potential. Using a transcriptome comparison of FoxJ1-null and wild-type microdissected tissue, we identified candidate genes regulated by FoxJ1 during early postnatal development. The list includes a significant number of microtubule-associated proteins, some of which form a protein complex that could regulate the transport of basal bodies to the ventricular surface of differentiating ependymal cells during FoxJ1-dependent ciliogenesis. Our results suggest that time-and cell-specific expression of FoxJ1 in the brain acts on an array of target genes to regulate the differentiation of ependymal cells and a small subset of astrocytes in the adult stem cell niche.

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Reinduction of ErbB2 in astrocytes promotes radial glial progenitor identity in adult cerebral cortex

Cited by 63 publications

References 86 publications

Capturing Changes in the Brain Microenvironment during Initial Steps of Breast Cancer Brain Metastasis

Capturing Changes in the Brain Microenvironment during Initial Steps of Breast Cancer Brain Metastasis

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

FoxJ1-dependent gene expression is required for differentiation of radial glia into ependymal cells and a subset of astrocytes in the postnatal brain

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