Stage-Specific Effects ofSonic HedgehogExpression in the Epidermis

Abstract

Sonic hedgehog (Shh) is expressed in the ectoderm of the forming hair follicle and feather bud during normal development. However, inappropriate activation of the Shh signal transduction cascade in human epidermis can cause basal cell carcinoma. Here we show that during normal development of avian skin, Shh is first expressed only after the responsiveness to this protein has been suppressed in most of the surrounding ectodermal cells. Forced expression of Shh in avian skin prior to this time causes a disorganized ectodermal proliferation. However, as skin begins to differentiate, the forced expression of Shh causes feather bud formation. Subsequently, expression of Shh in interfollicular epidermis has little or no morphological effect. Restricted responsiveness to Shh in developing skin has functional consequences for morphogenesis and may have important implications for cutaneous pathologies as well.

Hedgehog Signaling Regulates Sebaceous Gland Development

“…However, additional studies are needed to define the precise conditions required for Hedgehog-pathway-driven formation of this specialized cell type. Interestingly, ectopic expression of Shh in embryonic mouse skin is sufficient to drive the formation of basal cell carcinoma-like proliferations but not sebaceous glands, 44 in keeping with studies suggesting that both the timing 45 and level 46 of Hedgehog signaling activity are important determinants of skin phenotype. In addition to regulating normal sebaceous gland development, it will be interesting to ascertain whether Hedgehog signaling is involved in the formation of sebaceous gland tumors and hyperplasias.…”

Inhibition of Epithelial Ductal Branching in the Prostate by Sonic Hedgehog Is Indirectly Mediated by Stromal Cells

“…It is possible that the tissue responsiveness to Shh may change as development proceeds. Such stage-specific responsiveness of Shh has been described during normal development of avian skin (63). Alternatively, localized expression of Shh in the distal aspect of the epithelial bud (64) may yield different outcomes as compared with ubiquitous administration of Shh.…”

Sonic hedgehog signaling pathway in vertebrate epithelial appendage morphogenesis: perspectives in development and evolution

“…Overexpression of SHH by retroviral vectors or recombinant SHH protein causes the formation of extra-large feather buds and expanded feather domains ( fig. 3D, [12,13,15]). Patched (Ptc), a SHH receptor, is present predominantly in the underlying mesenchyme, but also in the epithelium.…”

“…2B). Misexpression of SHH was further analyzed by forced expression at different time [15]. When Shh was transduced prior to the time of feather induction, it caused disorganized epidermal proliferation.…”