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.
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
a) A knockout of the Wnt4 gene
b) A knockout of the Rspo1 gene
c) A knockout of the Sox9 gene
To determine which factors would lead to sex reversion in an XY mouse fetus, we need to consider the role of Wnt signaling in primary sex determination.
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 activates genes necessary for the development of the ovary and suppresses Sox9, which is required for testis development.
Therefore, the following factors would lead to sex reversion in an XY mouse fetus:
a) A knockout of the Wnt4 gene: This would prevent the activation of genes necessary for ovary development and could lead to testis development.
b) A knockout of the Rspo1 gene: Rspo1 is involved in stabilizing β catenin, so its knockout could disrupt β catenin activation and lead to testis development.
c) A knockout of the Sox9 gene: Sox9 is required for testis development. In the absence of Sox9, β catenin would not be suppressed, leading to activation of the ovarian pathway.
d) Pharmacological inhibition of β catenin: Inhibiting β catenin would prevent its activation of genes necessary for ovary development and could lead to testis development.
e) Use of a constitutively active β catenin: This would constantly activate genes necessary for ovary development, even in the presence of a Y chromosome, leading to sex reversion.
Therefore, options a, b, c, d, and e would all potentially lead to sex reversion in an XY mouse fetus.
To determine which options could lead to sex reversion in an XY mouse fetus, we need to understand the role of various factors involved in primary sex determination.
In the female pathway, low levels of Wnt4 and Rspo1 are maintained by the transcription factors Wt1, Lhx1, GATA4, and Sf1. These factors work together to suppress the expression of Sox9 and maintain the expression of β-catenin.
In the male pathway, the presence of a Y chromosome leads to elevated expression of Sox9, which then suppresses β-catenin and activates the testis-determining pathway.
Based on this information, the following options could lead to sex reversion in an XY mouse fetus:
a) A knockout of the Wnt4 gene: If Wnt4 is knocked out, there would be a lack of Wnt4 signaling, which is necessary for the ovary development pathway. This could lead to the activation of the testis-determining pathway and sex reversion.
b) A knockout of the Rspo1 gene: Similarly, if Rspo1 is knocked out, there would be a lack of Rspo1 signaling, which is necessary for stabilizing β-catenin. Without stable β-catenin, the ovary development pathway may not be activated, potentially resulting in sex reversion.
c) A knockout of the Sox9 gene: In the male pathway, Sox9 suppresses β-catenin and activates the testis-determining pathway. If Sox9 is knocked out, β-catenin may not be suppressed, leading to the activation of the ovary development pathway and potential sex reversion.
d) Pharmacological inhibition of β-catenin: If β-catenin is pharmacologically inhibited, it would prevent its transcriptional activation of genes necessary for the development of the ovary and suppression of Sox9. This could lead to the activation of the testis-determining pathway and sex reversion.
e) Use of a constitutively active β-catenin: If a constitutively active form of β-catenin is introduced, it would bypass the regulatory mechanisms of the ovary development pathway and potentially activate the testis-determining pathway, resulting in sex reversion.
Therefore, options a, b, c, d, and e could all potentially lead to sex reversion in an XY mouse fetus.