GORAB promotes embryonic lung maturation through antagonizing AKT phosphorylation, versican expression, and mesenchymal cell migration.

Embryonic development of the alveolar sac of the lung is dependent upon multiple signaling pathways to coordinate cell growth, migration, and the formation of the extracellular matrix. Here, we identify GORAB as a regulator of embryonic alveolar sac formation as genetically disrupting the Gorab gene in mice resulted in fatal saccular maturation defects characterized by a thickened lung mesenchyme. This abnormality is not associated with impairments in cellular proliferation and death, but aberrantly increased protein kinase B (AKT) phosphorylation, elevated Vcan transcription, and enhanced migration of mesenchymal fibroblasts.

RPGRIP1L is required for stabilizing epidermal keratinocyte adhesion through regulating desmoglein endocytosis.

Cilia-related proteins are believed to be involved in a broad range of cellular processes. Retinitis pigmentosa GTPase regulator interacting protein 1-like (RPGRIP1L) is a ciliary protein required for ciliogenesis in many cell types, including epidermal keratinocytes. Here we report that RPGRIP1L is also involved in the maintenance of desmosomal junctions between keratinocytes.

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

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.

Correction of Hair Shaft Defects through Allele-Specific Silencing of Mutant Krt75.

Dominant mutations in keratin genes can cause a number of inheritable skin disorders characterized by intraepidermal blistering, epidermal hyperkeratosis, or abnormalities in skin appendages, such as nail plate dystrophy and structural defects in hair. Allele-specific silencing of mutant keratins through RNA interference is a promising therapeutic approach for suppressing the expression of mutant keratins and related phenotypes in the epidermis. However, its effectiveness on skin appendages remains to be confirmed in vivo.

The ciliopathy gene Rpgrip1l is essential for hair follicle development.

The primary cilium is essential for skin morphogenesis through regulating the Notch, Wnt, and hedgehog signaling pathways. Prior studies on the functions of primary cilia in the skin were based on the investigations of genes that are essential for cilium formation. However, none of these ciliogenic genes has been linked to ciliopathy, a group of disorders caused by abnormal formation or function of cilia.