Gorab Is Required for Dermal Condensate Cells to Respond to Hedgehog Signals during Hair Follicle Morphogenesis

Liu Y, Snedecor ER, Choi YJ, Yang N, Zhang X, Xu Y, Han Y, Jones EC, Shroyer KR, Clark RA, Zhang L, Qin C, Chen J.

Abstract

       GORAB is a golgin that localizes predominantly at the Golgi apparatus and physically interacts with small guanosine triphosphatases.GORAB is ubiquitously expressed in mammalian tissues, including the skin. However, the biological function of this golgin in skin is unknown. Here, we report that disrupting the expression of the Gorab gene in mice results in hair follicle morphogenesis defects that were characterized by impaired follicular keratinocyte differentiation. This hair follicle phenotype was associated with markedly suppressed hedgehog (Hh) signaling pathway in dermal condensates in vivo. Gorab-deficient dermal mesenchymal cells also displayed a significantly reduced capability to respond to Hh pathway activation in vitro. Furthermore, we found that the formation of the primary cilium, a cellular organelle that is essential for the Hh pathway, was impaired in mutant dermal condensate cells, suggesting that Gorab may be required for the Hh pathway through facilitating the formation of primary cilia. Thus, data obtained from this study provided insight into the biological functions of Gorab during embryonic morphogenesis of the skin in which Hh signaling and primary cilia exert important functions.

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