Sonic Hedgehog modulates EGFR dependent proliferation of neural stem cells during late mouse embryogenesis through EGFR transactivation

Reinchisi, Gisela; Parada, Margarita; Lois, Pablo; Oyanadel, Claudia; Shaughnessy, Ronan; González, Alfonso; Palma, Verónica

doi:10.3389/fncel.2013.00166

Cited by 25 publications

(27 citation statements)

References 58 publications

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“…In addition, it has recently been shown that SHH induces transactivation of the epidermal-growth factor receptor (EGFR) and facilitates mitogenic signaling via the ERK1/2 pathway (Reinchisi et al, 2013). Changes in cell size upon SHH or cyclopamine treatment could also affect mitogenic activity by altering protein phosphorylation levels (Meyers et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Sonic hedgehog signaling regulates mode of cell division of early cerebral cortex progenitors and increases astrogliogenesis

Araújo

Schroeder

et al. 2014

Front. Cell. Neurosci.

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The morphogen Sonic Hedgehog (SHH) plays a critical role in the development of different tissues. In the central nervous system, SHH is well known to contribute to the patterning of the spinal cord and separation of the brain hemispheres. In addition, it has recently been shown that SHH signaling also contributes to the patterning of the telencephalon and establishment of adult neurogenic niches. In this work, we investigated whether SHH signaling influences the behavior of neural progenitors isolated from the dorsal telencephalon, which generate excitatory neurons and macroglial cells in vitro. We observed that SHH increases proliferation of cortical progenitors and generation of astrocytes, whereas blocking SHH signaling with cyclopamine has opposite effects. In both cases, generation of neurons did not seem to be affected. However, cell survival was broadly affected by blockade of SHH signaling. SHH effects were related to three different cell phenomena: mode of cell division, cell cycle length and cell growth. Together, our data in vitro demonstrate that SHH signaling controls cell behaviors that are important for proliferation of cerebral cortex progenitors, as well as differentiation and survival of neurons and astroglial cells.

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Section: Discussionmentioning

confidence: 99%

Sonic hedgehog signaling regulates mode of cell division of early cerebral cortex progenitors and increases astrogliogenesis

Araújo

Schroeder

et al. 2014

Front. Cell. Neurosci.

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“…The HH pathway may activate ERK1/2 by several mechanisms: 1) following SMO activation, in a GLI-independent manner, via unknown signaling events. These effects are blocked by cyclopamine [72,82]; 2) following GLI activation via unknown mechanisms; it is not known whether transcriptional activity of GLI is involved [88]; 3) following expression of GLIdependent target genes that activate downstream ERK1/2, such as PDGFR and IRS1 [70,79,113]; 4) through PTCH in a SMO-independent manner [128]; 5) transactivation of EGFR by SHH has also been described [112]. M a n u s c r i p t A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t A c c e p t e d M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t …”

Section: Combination Of Hh and Mek1/2-erk1/2 Inhibitorsmentioning

confidence: 93%

“…SHH mediates the activation of ERK1/2 signaling in radial glial cells during late neocortex development and in Hela cells through EGFR transactivation [112] (Figure 2). …”

Section: Glioblastomamentioning

confidence: 98%

Mitogen-activated protein kinases and Hedgehog-GLI signaling in cancer: A crosstalk providing therapeutic opportunities?

Rovida

Stecca

2015

Seminars in Cancer Biology

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“…SHH can transactivate the EGF receptor (EGFR) [105]. In addition, EGF activates the RAS-MEK cascade and this can superactivate GLI1 [65].…”

Section: Regulation Of the Gli Code By Non-hh Signals And By The Oncomentioning

confidence: 99%

Context-dependent signal integration by the GLI code: The oncogenic load, pathways, modifiers and implications for cancer therapy

Aberger

Altaba

2014

Seminars in Cell & Developmental Biology

146

175

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Canonical Hedgehog (HH) signaling leads to the regulation of the GLI code: the sum of all positive and negative functions of all GLI proteins. In humans, the three GLI factors encode context-dependent activities with GLI1 being mostly an activator and GLI3 often a repressor. Modulation of GLI activity occurs at multiple levels, including by co-factors and by direct modification of GLI structure. Surprisingly, the GLI proteins, and thus the GLI code, is also regulated by multiple inputs beyond HH signaling. In normal development and homeostasis these include a multitude of signaling pathways that regulate proto-oncogenes, which boost positive GLI function, as well as tumor suppressors, which restrict positive GLI activity. In cancer, the acquisition of oncogenic mutations and the loss of tumor suppressors – the oncogenic load – regulates the GLI code toward progressively more activating states. The fine and reversible balance of GLI activating GLIA and GLI repressing GLIR states is lost in cancer. Here, the acquisition of GLIA levels above a given threshold is predicted to lead to advanced malignant stages. In this review we highlight the concepts of the GLI code, the oncogenic load, the context-dependency of GLI action, and different modes of signaling integration such as that of HH and EGF. Targeting the GLI code directly or indirectly promises therapeutic benefits beyond the direct blockade of individual pathways.

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Sonic Hedgehog modulates EGFR dependent proliferation of neural stem cells during late mouse embryogenesis through EGFR transactivation

Cited by 25 publications

References 58 publications

Sonic hedgehog signaling regulates mode of cell division of early cerebral cortex progenitors and increases astrogliogenesis

Sonic hedgehog signaling regulates mode of cell division of early cerebral cortex progenitors and increases astrogliogenesis

Mitogen-activated protein kinases and Hedgehog-GLI signaling in cancer: A crosstalk providing therapeutic opportunities?

Context-dependent signal integration by the GLI code: The oncogenic load, pathways, modifiers and implications for cancer therapy

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