Differential expression of WNT4 in testicular and ovarian development in a marsupial.
BACKGROUND
WNT4 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 in gonads.


RESULTS
Before 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.


CONCLUSIONS
This 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.
Yu
Hongshi
H
Department of Zoology, The University of Melbourne, Victoria 3010, Australia. hongshiy@unimelb.edu.au
Pask
Andrew J
AJ
Shaw
Geoffrey
G
Renfree
Marilyn B
MB
D000595:Amino Acid Sequence; D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D007150:Immunohistochemistry; D007614:Macropodidae / Q000196:embryology / Q000235:genetics* / Q000254:growth & development; D008297:Male; D008969:Molecular Sequence Data; D010053:Ovary / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D010802:Phylogeny; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D013997:Time Factors; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D060528:Wnt4 Protein
D018076:DNA, Complementary; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C555581:WNT4 protein, human; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; D004247:DNA