Role of Sox2 in the development of the mouse neocortex

Bani‐Yaghoub, Mahmud; Tremblay, Roger; Lei, Joy X; Zhang, Dongling; Zurakowski, Bogdan; Sandhu, Jagdeep K.; Smith, Brandon; Ribecco-Lutkiewicz, Maria; Kennedy, Jessica A.; Walker, P. Roy; Sikorska, Marianna

doi:10.1016/j.ydbio.2006.03.007

Cited by 242 publications

(241 citation statements)

References 89 publications

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“…Here we demonstrate that this probably occurs through induction of Sox2. This is in contrast to the eye and neocortex, where it has been shown that Sox2 appears to act upstream of Notch signaling (9,18). However, the demonstration that inhibition of Notch signaling within an existing prosensory domain leads to down-regulation of Sox2 expression suggests that the role of Notch in Sox2 expression extends beyond the period of Sox2 induction.…”

Section: Discussionmentioning

confidence: 87%

Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea

Dabdoub

Puligilla

Jones

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

311

421

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Sox2 is a high-mobility transcription factor that is one of the earliest markers of developing inner ear prosensory domains. In humans, mutations in SOX2 cause sensorineural hearing loss and a loss of function study in mice showed that Sox2 is required for prosensory formation in the cochlea. However, the specific roles of Sox2 have not been determined. Here we illustrate a dynamic role of Sox2 as an early permissive factor in prosensory domain formation followed by a mutually antagonistic relationship with Atoh1, a bHLH protein necessary for hair cell development. We demonstrate that decreased levels of Sox2 result in precocious hair cell differentiation and an over production of inner hair cells and that these effects are likely mediated through an antagonistic interaction between Sox2 and the bHLH molecule Atoh1. Using gain-and loss-of-function experiments we provide evidence for the molecular pathway responsible for the formation of the cochlear prosensory domain. Sox2 expression is promoted by Notch signaling and Prox1, a homeobox transcription factor, is a downstream target of Sox2. These results demonstrate crucial and diverse roles for Sox2 in the development, specification, and maintenance of sensory cells within the cochlea.development ͉ organ of Corti ͉ inner ear ͉ HMG box ͉ bHLH T he sensory epithelium of the mammalian cochlea (the organ of Corti) develops from a pool of prosensory cells derived from the ventral region of the otocyst. Proper development of the cochlea requires that cochlear progenitor cells transition through states of developmental competence, coordinated cell cycle exit, and cell fate specification and differentiation to generate the distinctly fated cell populations within the highly ordered mosaic of the organ of Corti (1). The signal transduction pathways that coordinate cochlear prosensory specification are only beginning to be identified. Moreover, since these signal transduction pathways are unlikely to be linear cascades, it will also be necessary to determine how different pathways are organized into complex signaling networks that ultimately generate precise and unique responses within individual cochlear prosensory cells.Sox (SRY related HMG box) proteins are a group of transcription factors that regulate diverse developmental processes; for instance, Sox2 is a universal marker of stem cells and is also expressed in neural progenitor cells at different stages of central nervous system development. Sox2, along with Sox1 and Sox3, comprise the SoxB1 group. Members of this group are thought to maintain neural precursor cells in a progenitor state by inhibiting bHLH-mediated neuronal differentiation (2). Reciprocally, bHLH proteins must suppress expression and activity of SoxB1 proteins to induce cellular differentiation. A recent loss-of-function study demonstrated that Sox2 is required for development of sensory epithelia, including the organ of Corti, within the inner ear (3). However, despite its absolute necessity for the formation of inner ear sensory epithelia, the spe...

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Section: Discussionmentioning

confidence: 87%

Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea

Dabdoub

Puligilla

Jones

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

311

421

View full text Add to dashboard Cite

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“…For example, progenitors in the VZ at early stages of corticogenesis express a number of transcription factors (such as Fezf2, Otx1, Sox2, and Emx2) that are maintained by their progeny as young neurons populate the deep layers [11][12][13][14]. However, at middle stages of neurogenesis, as progenitors begin to produce the neurons of layers 4 through 2, the cells undergo a series of interesting cellular and molecular alterations.…”

Section: Cellular Studies Of Cell Fate Determination Suggest a Progrementioning

confidence: 99%

The determination of projection neuron identity in the developing cerebral cortex

Leone

Srinivasan

Chen

et al. 2008

Current Opinion in Neurobiology

334

316

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Here we review the mechanisms that determine projection neuron identity during cortical development. Pyramidal neurons in the mammalian cerebral cortex can be classified into two major classes: corticocortical projection neurons, which are concentrated in the upper layers of the cortex, and subcortical projection neurons, which are found in the deep layers. Early progenitor cells in the ventricular zone produce deep layer neurons that express transcription factors including Sox5, Fezf2, and Ctip2, which play important roles in the specification of subcortically projecting axons. Upper layer neurons are produced from progenitors in the subventricular zone, and the expression of Satb2 in these differentiating neurons is required for the formation of axonal projections that connect the two cerebral hemispheres. The Fezf2/Ctip2 and Satb2 pathways appear to be mutually repressive, thus ensuring that individual neurons adopt either a subcortical or callosal projection neuron identity at early times during development. The molecular mechanisms by which Satb2 regulates gene expression involves long-term epigenetic changes in chromatin configuration, which may enable cell fate decisions to be maintained during development.

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“…Coupling of angiogenesis and neurogenesis after stroke H Teng et al in the levels of Sox2 mRNA, a gene involved in the maintenance of neural progenitor cell identity (Bani-Yaghoub et al, 2006;Graham et al, 2003), and an increase in the levels of Hes6 mRNA, a gene that promotes neuronal differentiation but inhibits astrocyte differentiation (Gratton et al, 2003;Jhas et al, 2006) (Figure 3). However, when normal SVZ cells were cocultured with stroke RBECs in the growth or differentiation medium in the presence of SU1498, a VEGFR2 antagonist, the number of BrdU + (Figures 2C to E) and Tuj1 + ( Figures 2I, 2J, and 2O) cells was significantly reduced, while the number of GFAP + cells did not significantly change (26.8% ± 1.8% versus 23.5% ± 4.0% in the SU1498 group, Figures 2M, 2N, and 2P).…”

Section: Endothelial Cells Activated By Stroke Increase Proliferationmentioning

confidence: 99%

Coupling of Angiogenesis and Neurogenesis in Cultured Endothelial Cells and Neural Progenitor Cells after Stroke

Hua

Zhang

Wang

et al. 2007

J Cereb Blood Flow Metab

228

176

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Angiogenesis and neurogenesis are coupled processes. Using a coculture system, we tested the hypothesis that cerebral endothelial cells activated by ischemia enhance neural progenitor cell proliferation and differentiation, while neural progenitor cells isolated from the ischemic subventricular zone promote angiogenesis. Coculture of neural progenitor cells isolated from the subventricular zone of the adult normal rat with cerebral endothelial cells isolated from the stroke boundary substantially increased neural progenitor cell proliferation and neuronal differentiation and reduced astrocytic differentiation. Conditioned medium harvested from the stroke neural progenitor cells promoted capillary tube formation of normal cerebral endothelial cells. Blockage of vascular endothelial growth factor receptor 2 suppressed the effect of the endothelial cells activated by stroke on neurogenesis as well as the effect of the supernatant obtained from stroke neural progenitor cells on angiogenesis. These data suggest that angiogenesis couples to neurogenesis after stroke and vascular endothelial growth factor likely mediates this coupling.

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Role of Sox2 in the development of the mouse neocortex

Cited by 242 publications

References 89 publications

Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea

Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea

The determination of projection neuron identity in the developing cerebral cortex

Coupling of Angiogenesis and Neurogenesis in Cultured Endothelial Cells and Neural Progenitor Cells after Stroke

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