Abstract
BackgroundWNT4 is a key regulator of gonadal differentiation in humans and mice, playing a pivotal role in early embryogenesis. Using a marsupial, the tammar wallaby, in which most gonadal differentiation occurs after birth whilst the young is in the pouch, we show by quantitative PCR during early testicular and ovarian development that WNT4 is differentially expressed ingonads.ResultsBefore birth, WNT4 mRNA expression was similar in indifferent gonads of both sexes. After birth, in females WNT4 mRNA dramatically increased during ovarian differentiation, reaching a peak by day 9–13 post partum (pp) when the ovarian cortex and medulla are first distinguishable. WNT4 protein was localised in the ovarian cortex and at the medullary boundary. WNT4 mRNA then steadily decreased to day 49, by which time all the female germ cells have entered meiotic arrest. In males, WNT4 mRNA was down-regulated in testes immediately after birth, coincident with the time that seminiferous cords normally form, and rose gradually after day 8. By day 49, when testicular androgen production normally declines, WNT4 protein was restricted to the Leydig cells.ConclusionThis is the first localisation of WNT4 protein in developing gonads and is consistent with a role for WNT4 in steroidogenesis. Our data provide strong support for the suggestion that WNT4 not only functions as an anti-testis gene during early development, but is also necessary for later ovarian and testicular function.
Highlights
WNT4 is a key regulator of gonadal differentiation in humans and mice, playing a pivotal role in early embryogenesis
Cloning and characterization of the tammar WNT4 Gene Sequence analysis confirmed that PCR products were derived from the WNT4 gene
Using the PHYLIP 3.63 program to construct a phylogenetic tree analysis of WNT4 proteins, tammar wallaby WNT4 clusters with eutherian mammals whereas chicken and frog form another group, zebrafish and Amphioxus produce different branches, C. elegans and fruit fly create another group distantly related to vertebrates (Fig. 2b)
Summary
WNT4 is a key regulator of gonadal differentiation in humans and mice, playing a pivotal role in early embryogenesis. WNT4 plays a pivotal role in early embryogenesis, in the formation of the urogenital system [1,2,3,4]. After the action of Sry in the XY gonad Wnt expression decreases to undetectable levels in the developing testis, but remains at high levels in the ovary [4]. This led to the initial hypothesis that WNT4 acts as an anti-testis gene, blocking Leydig cell differentiation and steroidogenesis in the developing ovary [4].
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