Hedgehog signaling promotes endoneurial fibroblast migration and Vegf-A expression following facial nerve injury

Faniku, Chrysovalantou; Kong, Wuyi; He, Liang; Zhang, M.; Lilly, Gabriela L.; Pepper, Jon‐Paul

doi:10.1016/j.brainres.2020.147204

Cited by 6 publications

(4 citation statements)

References 48 publications

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“…This pro-angiogenic effect is believed to be mediated by HIF-1a signaling (Chen et al, 2020). Additionally, a recent report identified Gli1-expressing EFs as a source of VEGF in the setting of nerve injury (Faniku et al, 2021). Our data are consistent with this possibility given the close association of the EF-derived MFs and the vasculature (Fig.…”

Section: Gli1 Demarcates Peripheral Nerve Pericytes and Regulates Vas...supporting

confidence: 88%

Gli1 Regulates the Postnatal Acquisition of Peripheral Nerve Architecture

et al. 2021

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Peripheral nerves are organized into discrete compartments. Axons, Schwann cells (SCs), and endoneurial fibroblasts (EFs) reside within the endoneurium and are surrounded by the perineurium, a cellular sheath comprised of layers of perineurial glia (PNG). SC secretion of Desert Hedgehog (Dhh) regulates this organization. In Dhh nulls, the perineurium is deficient and the endoneurium is subdivided into small compartments termed minifascicles. Human Dhh mutations cause a neuropathy with similar defects.Here we examine the role of Gli1, a canonical transcriptional effector of hedgehog signaling, in regulating peripheral nerve organization in mice of both genders. We identify PNG, EFs, and pericytes as Gli1-expressing cells by genetic fate mapping. Although expression of Dhh by SCs and Gli1 in target cells is coordinately regulated with myelination, Gli1 expression unexpectedly persists in Dhh null EFs. Thus, Gli1 is expressed in EFs noncanonically (i.e., independent of hedgehog signaling). Gli1 and Dhh also have nonredundant activities. Unlike Dhh nulls, Gli1 nulls have a normal perineurium. Like Dhh nulls, Gli1 nulls form minifascicles, which we show likely arise from EFs. Thus, Dhh and Gli1 are independent signals: Gli1 is dispensable for perineurial development but functions cooperatively with Dhh to drive normal endoneurial development. During development, Gli1 also regulates endoneurial extracellular matrix production, nerve vascular organization, and has modest, nonautonomous effects on SC sorting and myelination of axons. Finally, in adult nerves, induced deletion of Gli1 is sufficient to drive minifascicle formation. Thus, Gli1 regulates the development and is required to maintain the endoneurial architecture of peripheral nerves.

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Section: Gli1 Demarcates Peripheral Nerve Pericytes and Regulates Vas...supporting

confidence: 88%

Gli1 Regulates the Postnatal Acquisition of Peripheral Nerve Architecture

et al. 2021

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Section: Gli1 Demarcates Peripheral Nerve Pericytes and Regulates Vascular Organizationsupporting

confidence: 87%

Gli1 regulates the postnatal acquisition of peripheral nerve architecture

Zotter

Dagan

Brady

et al. 2021

Preprint

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Peripheral nerves are organized into discrete cellular compartments. Axons, Schwann cells (SCs), and endoneurial fibroblasts (EFs) reside within the endoneurium and are surrounded by the perineurium - a cellular sheath comprised of layers of perineurial glia (PNG). SC secretion of Desert Hedgehog (Dhh) regulates this organization. In Dhh nulls, the perineurium is deficient and the endoneurium is subdivided into small compartments termed minifascicles. Human Dhh mutations cause a peripheral neuropathy with similar defects. Here we examine the role of Gli1, a canonical transcriptional effector of hedgehog signaling, in regulating peripheral nerve organization. We identify PNG, EFs, and pericytes as Gli1-expressing cells by genetic fate mapping. Although expression of Dhh by SCs and Gli1 in target cells is coordinately regulated with myelination, Gli1 expression unexpectedly persists in Dhh null EFs. Thus, Gli1 is expressed in EFs non-canonically i.e., independent of hedgehog signaling. Gli1 and Dhh also have non-redundant activities. In contrast to Dhh nulls, Gli1 nulls have a normal perineurium. Like Dhh nulls, Gli1 nulls form minifascicles, which we show likely arise from EFs. Thus, Dhh and Gli1 are independent signals: Gli1 is dispensable for perineurial development but functions cooperatively with Dhh to drive normal endoneurial development. During development, Gli1 also regulates endoneurial extracellular matrix production, nerve vascular organization, and has modest, non-autonomous effects on SC sorting and myelination of axons. Finally, in adult nerves, induced deletion of Gli1 is sufficient to drive minifascicle formation. Thus, Gli1 regulates the development and is required to maintain the endoneurial architecture of peripheral nerves.

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“…Vascular endothelial growth factor (VEGF) stimulates the angiogenesis needed for tumor growth, invasion, and metastasis [ 134 ]. VEGF expression under certain conditions is regulated by the Hh pathway [ 135 ]. Recent studies also demonstrated direct oncogenic effects of VEGF, which alters keratinocyte survival and proliferation to favor NMSC development [ 136 ].…”

Section: Investigational Drugsmentioning

confidence: 99%

Advances in Management and Therapeutics of Cutaneous Basal Cell Carcinoma

Chen

Kim²,

Steele³

et al. 2022

Cancers

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Basal cell carcinoma (BCC), the most common cancer in humans, is a malignant neoplasm of cells derived from the basal layer of the epidermis. Tumor characteristics such as histologic subtype, primary versus recurrent tumor, anatomic location, size, and patient attributes determine the risk level and acceptable treatment options. Surgical options offer histologic confirmation of tumor clearance. Standard excision provides post-treatment histologic assessment, while Mohs micrographic surgery (MMS) provides complete margin assessment intraoperatively. Additional treatment options may be employed in the correct clinical context. Small and low-risk BCCs, broad field cancerization, locally-advanced disease, metastatic disease, cosmetic concerns, or morbidity with surgical approaches raise consideration of other treatment modalities. We review herein a range of treatment approaches and advances in treatments for BCC, including standard excision, MMS, electrodesiccation and curettage, ablative laser treatment, radiation therapy, targeted molecular therapies, topical therapies, field therapies, immunotherapy, and experimental therapies.

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Hedgehog signaling promotes endoneurial fibroblast migration and Vegf-A expression following facial nerve injury

Cited by 6 publications

References 48 publications

Gli1 Regulates the Postnatal Acquisition of Peripheral Nerve Architecture

Gli1 Regulates the Postnatal Acquisition of Peripheral Nerve Architecture

Gli1 regulates the postnatal acquisition of peripheral nerve architecture

Advances in Management and Therapeutics of Cutaneous Basal Cell Carcinoma

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