Models for how Wnt4a functions to promote female development. (A) In wild-type animals, high concentrations of a signal produced by early stage oocytes during the bipotential gonad stage (purple →) likely cause the gonadal soma to maintain production of estrogen (black →), which inhibits oocyte death and drives female sex determination. If the oocyte signal is too low, a male develops; if the signal exceeds a threshold, a female develops. In a wild-type population, this threshold and signal gradient produces about half males and half females. In A–C, the x-axis depicts the strength of the signal while the y-axis plots the numbers of animals that produce a certain amount of signal. For simplicity, signal strength vs. fish number is assumed to follow a normal distribution. Color intensity reflects the probability an individual develops as a male (blue) or female (red). (B) In this model, lack of Wnt4a desensitizes somatic gonad cells to the female-promoting oocyte signal, thereby raising the female-development threshold such that only those few wnt4a mutant animals that produce the highest signal (perhaps stochastically) can develop as females, allowing most to become males. (C) Alternatively, lack of Wnt4a causes oocytes to decrease the amount of female-promoting signal that they produce, such that fewer wnt4a mutants achieve the level required to sustain female development. Insets in B and C are graphical representations of the two models (oocyte in pink, somatic gonad cell in red or blue).