Wnt signaling contributes the greatest impact in primary sex determination in the female. In the absence of a Y chromosome, low levels of Wnt and R-spondin 1 (Rspo1) are maintained by the transcription factors Wt1, Lhx1, GATA4 and Sf1. Wnt4 and Rspo1 can independently signal through different pathways to stabilize β catenin. β catenin, in turn, transcriptionally activates the genes that encode for Wnt4 and Rspo1, setting up a positive feedback loop.

Question

β catenin activates genes necessary for the development of the ovary and suppresses Sox9, which is required for testis development. In the presence of a Y chromosome, Sox9 expression is elevated, which suppresses β catenin and leads to the activation of the testis-determining pathway.
Which of the following would lead to a sex reversion in an XY mouse fetus? Select ALL that apply.
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a
A knockout of the Wnt4 gene

b
A knockout of the Rspo1 gene

c
A knockout of the Sox9 gene

d
Pharmacological inhibition of β catenin

e
Use of a constitutively active β catenin

Answer 1

a) A knockout of the Wnt4 gene
b) A knockout of the Rspo1 gene
c) A knockout of the Sox9 gene