Reagents for developmental regulation of Hedgehog signaling

Lewis, Cristy; Krieg, Paul A.

doi:10.1016/j.ymeth.2013.08.022

Cited by 15 publications

(12 citation statements)

References 27 publications

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“…Moreover, Xenopus embryos are easily treated with chemical modulators. Thus, early effects of Hh perturbation can be readily bypassed (Hollemann et al, 2007; Lewis and Krieg, 2014; Peyrot et al, 2011). We asked whether Hh loss of function, using the potent inhibitor cyclopamine or SANT1, could perturb primary mouth development (Chen et al, 2002; Peyrot et al, 2011; Williams et al, 2003).…”

Section: Resultsmentioning

confidence: 99%

Hedgehog activity controls opening of the primary mouth

Tabler

Bolger

Wallingford

et al. 2014

Developmental Biology

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To feed or breathe, the oral opening must connect with the gut. The foregut and oral tissues converge at the primary mouth, forming the buccopharyngeal membrane (BPM), a bilayer epithelium. Failure to form the opening between gut and mouth has significant ramifications, and many craniofacial disorders have been associated with defects in this process. Oral perforation is characterized by dissolution of the BPM, but little is known about this process. In humans, failure to form a continuous mouth opening is associated with mutations in Hedgehog (Hh) pathway members; however, the role of Hh in primary mouth development is untested. Here, we show, using Xenopus, that Hh signaling is necessary and sufficient to initiate mouth formation, and that Hh activation is required in a dose-dependent fashion to determine the size of the mouth. This activity lies upstream of the previously demonstrated role for Wnt signal inhibition in oral perforation. We then turn to mouse mutants to establish that SHH and Gli3 are indeed necessary for mammalian mouth development. Our data suggest that Hh-mediated BPM persistence may underlie oral defects in human craniofacial syndromes.

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Section: Resultsmentioning

confidence: 99%

Hedgehog activity controls opening of the primary mouth

Tabler

Bolger

Wallingford

et al. 2014

Developmental Biology

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“…Tamoxifen was administered intraperitoneally for 2 days (200 mg/kg, Sigma‐Aldrich, St. Louis, MO, USA) and lesioning was performed 14 days after the last tamoxifen injection. To inhibit Shh signaling in vivo , we injected intraperitoneally specific antagonist cyclopamine (Cyc, 25 mg/kg, LKT Laboratories, St. Paul, MN, USA (Chen et al, ) for 7 days and to activate Shh signaling we used the same injection protocol using selective Smoothened agonist [SAG, 20 mg/kg, VDM Biochemicals, Bedford Heights, OH, USA (Lewis and Krieg, )].…”

Section: Methodsmentioning

confidence: 99%

Generation of reactive astrocytes from NG2 cells is regulated by sonic hedgehog

Honsa

Valný

Kriška

et al. 2016

Glia

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NG2 cells, a fourth glial cell type in the adult mammalian central nervous system, produce oligodendrocytes in the healthy nervous tissue, and display wide differentiation potential under pathological conditions, where they could give rise to reactive astrocytes. The factors that control the differentiation of NG2 cells after focal cerebral ischemia (FCI) are largely unknown. Here, we used transgenic Cspg4-cre/Esr1/ROSA26Sortm14(CAG-tdTomato) mice, in which tamoxifen administration triggers the expression of red fluorescent protein (tomato) specifically in NG2 cells and cells derived therefrom. Differentiation potential (in vitro and in vivo) of tomato-positive NG2 cells from control or postischemic brains was determined using the immunohistochemistry, single cell RT-qPCR and patch-clamp method. The ischemic injury was induced by middle cerebral artery occlusion, a model of FCI. Using genetic fate-mapping method, we identified sonic hedgehog (Shh) as an important factor that influences differentiation of NG2 cells into astrocytes in vitro. We also manipulated Shh signaling in the adult mouse brain after FCI. Shh signaling activation significantly increased the number of astrocytes derived from NG2 cells in the glial scar around the ischemic lesion, while Shh signaling inhibition caused the opposite effect. Since Shh signaling modifications did not change the proliferation rate of NG2 cells, we can conclude that Shh has a direct influence on the differentiation of NG2 cells and therefore, on the formation and composition of a glial scar, which consequently affects the degree of the brain damage. GLIA 2016;64:1518-1531.

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“…82 Some scholars reported that cyclopamine, a specific blocker of the Hh signaling pathway, can effectively block the transcription of Gli1 mRNA to significantly weaken cellular invasiveness and adhesive ability. 83 Zhang et al 84 found that the new Hh inhibitor CUR-0199691 possesses an inhibitory function against breast cancer cells. Other studies have reported that dexamethasone can inhibit the TGF-induced EMT and the migration of cells, which prevents tumor metastasis.…”

Section: Role Of Emt In Chemoresistance and Anti-cancer Therapymentioning

confidence: 99%