A Cre knockin mouse reveals specific expression of Agouti gene in mesenchymal lineage cells in multiple organs and provides a unique tool for conditional gene targeting.

The mouse Agouti gene encodes a paracrine signaling factor which promotes melanocytes to produce yellow instead of black pigment. It has been reported that Agouti mRNA is confined to the dermal papilla after birth in various mammalian species. In this study, we created and characterized a knockin mouse strain in which Cre recombinase was expressed in-frame with endogenous Agouti coding sequence. The Agouti-Cre mice were bred with reporter mice (Rosa26-tdTomato or Rosa26-ZsGreen) to trace the lineage of Agouti-expressing cells during development. In skin, the reporter was detected in some dermal fibroblasts at the embryonic stage and in all dermal fibroblasts postnatally. It was also expressed in all mesenchymal lineage cells in other organs/tissues, including eyes, tongue, muscle, intestine, adipose, prostate and testis. Interestingly, the reporter expression was excluded from epithelial cells in the above organs/tissues. In brain, the reporter was observed in the outermost meningeal fibroblasts. Our work helps to illustrate the Agouti expression pattern during development and provides a valuable mouse strain for conditional gene targeting in mesenchymal lineage cells in multiple organs.

Spatial association of SEMA3C with nerve endings/terminal Schwann cells in hair follicle isthmus region.

Nerve endings and terminal Schwann cells (TSCs) specifically and densely surround hair follicle at isthmus area, forming a neuromuscular-junction-like structure called lanceolate complex. The interplay between neuronal components and epidermis in this specialized structure enables hair to properly sense complex stimuli from environments. However, how nerves precisely attach to and innervate this specific region during development remains to be elucidated. Here, we demonstrate that SEMA3C, a secreted protein member of semaphorin family responsible for axonal guidance, is localized right below sebaceous gland and in close approximation with nerve endings and TSCs processes all through the entire hair cycle. SEMA3C protein is deposited outside of epithelial cells and its expression is independent on the presence of nerve endings/TSCs. SEMA3C is also found in portions of dermal papilla at growth phase. The tight spatial association of SEMA3C with lanceolate complex suggests that it might play roles in establishment and/or maintenance of the lanceolate complex in hair follicle.