title: R-spondin1 and FOXL2 act into two distinct cellular types during goat ovarian differentiation.
abstract: BACKGROUND
  Up 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.
  
  
  RESULTS
  Similarly 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).
  
  
  CONCLUSIONS
  During 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.
authors.affiliation: INRA, UMR 1198, ENVA, CNRS, FRE 2857, Biologie du Développement et de la Reproduction, Jouy-en-Josas, F-78350, France. Ayhan.Kocer@jouy.inra.fr
authors.forename: Ayhan
authors.initials: A
authors.lastname: Kocer
authors.forename: Iris
authors.initials: I
authors.lastname: Pinheiro
authors.forename: Maëlle
authors.initials: M
authors.lastname: Pannetier
authors.forename: Lauriane
authors.initials: L
authors.lastname: Renault
authors.forename: Pietro
authors.initials: P
authors.lastname: Parma
authors.forename: Orietta
authors.initials: O
authors.lastname: Radi
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Kim
authors.forename: Giovanna
authors.initials: G
authors.lastname: Camerino
authors.forename: Eric
authors.initials: E
authors.lastname: Pailhoux
mesh_terms: D000818:Animals; D018076:DNA, Complementary; D012734:Disorders of Sex Development; D004622:Embryo, Mammalian / Q000166:cytology / Q000502:physiology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006041:Goats / Q000196:embryology / Q000235:genetics* / Q000502:physiology; D016366:Open Reading Frames; D010053:Ovary / Q000196:embryology*; D010802:Phylogeny; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012733:Sex Differentiation / Q000235:genetics*; D019699:Thrombospondins / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D051858:Forkhead Transcription Factors; D019699:Thrombospondins