Expression Of Rspo1 Research Articles

An X-Linked Body Color Gene of the Frog Rana rugosa and Its Application to the Molecular Analysis of Gonadal Sex Differentiation

We identified a sex-linked, recessive body color gene, presently designated w (whitish-yellow), in the frog Rana rugosa from the Iwakuni population in Western Japan. This is the first time a sex-linked body color gene was found in amphibians so far. In this population of R. rugosa, males are the heterogametic sex, but the sex chromosomes are still homomorphic. When heterozygous males (Ww), which were produced by crossing a whitish-yellow female (ww) found in the field and a wild-type male (WW) of the same population, were backcrossed to the homozygous whitish-yellow female (ww), the resultant male offspring were all wild-type, whereas the females were all whitish-yellow. This result definitely indicates that w is recessive and X-linked, and its wild-type allele W is located on the Y chromosome. Using this strain (X^wX^w female and X^wY^W male), we found that expression of Dmrt1 and Rspo1, which are involved in testicular and ovarian differentiation in vertebrates, was higher in males and females, respectively, prior to the onset of the sexually dimorphic expression of Cyp17 and Cyp19, which are involved in biosynthesis of sex steroids and are critical markers of gonadal sex differentiation.

The Role of R-Spondin2 in Keratinocyte Proliferation and Epidermal Thickening in Keloid Scarring

Keloids are found only in humans and the underlying biochemical mechanisms of their pathogenesis remain unknown. R-spondins (Rspos) are a relatively new group of secreted proteins known to be Wnt/β-catenin signaling agonists, but their role in keloids has yet to be elucidated. We investigated the expression levels of R-spondin2 (Rspo2) in cell lysates and conditioned media of monocultures and co-cultures of fibroblasts and keratinocytes derived from keloids and normal skin. In this study we found increased protein expression and secretion of Rspo2 in respective monocultures of keloid fibroblasts and keratinocytes when compared with their normal counterparts. Double-chamber co-culture experiments implicated the role of keloid keratinocytes (KKs) in the induction of Rspo2 secretion from fibroblasts because of epithelial-mesenchymal interactions. Addition of recombinant human Rspo2 in culture increased the proliferation of keratinocytes and it acted synergistically with Wnt3a through the canonical Wnt/β-catenin pathway. Overexpression of Rspo2 in normal fibroblasts brought about thicker epidermis when compared with control fibroblasts in a skin organotypic culture model. This observation coincides with the hyperproliferative phenotype of thickened epidermis seen in keloids. Taken together, the results suggest the possible double paracrine action of KKs in inducing higher expression of Rspo2 in fibroblasts that promotes keratinocyte proliferation and epidermal thickening.

R-spondin1 and FOXL2act into two distinct cellular types during goat ovarian differentiation

BackgroundUp to now, two loci have been involved in XX sex-reversal in mammals following loss-of-function mutations, PIS (Polled Intersex Syndrome) in goats and R-spondin1 (RSPO1) in humans. Here, we analyze the possible interaction between these two factors during goat gonad development. Furthermore, since functional redundancy between different R-spondins may influence gonad development, we also studied the expression patterns of RSPO2, 3 and 4.ResultsSimilarly to the mouse, RSPO1 shows a sex-dimorphic expression pattern during goat gonad development with higher levels in the ovaries. Interestingly, the PIS mutation does not seem to influence its level of expression. Moreover, using an RSPO1 specific antibody, the RSPO1 protein was localized in the cortical area of early differentiating ovaries (36 and 40 dpc). This cortical area contains the majority of germ cell that are surrounded by FOXL2 negative somatic cells. At latter stages (50 and 60 dpc) RSPO1 protein remains specifically localized on the germ cell membranes. Interestingly, a time-specific relocation of RSPO1 on the germ cell membrane was noticed, moving from a uniform distribution at 40 dpc to a punctuated staining before and during meiosis (50 and 60 dpc respectively). Interestingly, also RSPO2 and RSPO4 show a sex-dimorphic expression pattern with higher levels in the ovaries. Although RSPO4 was found to be faintly and belatedly expressed, the expression of RSPO2 increases at the crucial 36 dpc stage, as does that of FOXL2. Importantly, RSPO2 expression appears dramatically decreased in XX PIS-/- gonads at all three tested stages (36, 40 and 50 dpc).ConclusionDuring goat ovarian development, the pattern of expression of RSPO1 is in agreement with its possible anti-testis function but is not influenced by the PIS mutation. Moreover, our data suggest that RSPO1 may be associated with germ cell development and meiosis. Interestingly, another RSPO gene, RSPO2 shows a sex-dimorphic pattern of expression that is dramatically influenced by the PIS mutation.