Foxl2functions in sex determination and histogenesis throughout mouse ovary development

Abstract

Background: Partial loss of function of the transcription factor FOXL2 leads to premature ovarian failure in women. In animal models, Foxl2 is required for maintenance, and possibly induction, of female sex determination independently of other critical genes, e.g., Rspo1. Here we report expression profiling of mouse ovaries that lack Foxl2 alone or in combination with Wnt4 or Kit/c-Kit.

FOXL2 versus SOX9: A lifelong “battle of the sexes”

“…The reports by Uhlenhaut et al [1] and Garcia-Ortiz et al [2] clearly show that early ovarian development and maintenance do not rely on a passive pathway. Indeed, the ovary is permanently struggling against transdifferentiation.…”

“…[2,26] Interestingly, Foxl2 single mutants do not show this molecular phenotype that early. However, it is known that Foxl2 ablation up-regulates Sox9 expression postnatally.…”

“…At present it is not clear whether Wnt4 and Foxl2 signals are convergent or complementary. [1,2,39] Thus, if, on the contrary, some of these signals act as activators, and some as repressors, the system would form an incoherent feed-forward loop, a device for driving an outcome that depends on the fold change in the input signal, and not on its absolute level. [40,41] Further studies are required on this whole subject.…”

“…Both Uhlenhaut et al [1] and Garcia-Ortiz et al [2] claim, on justified grounds, that there is a masculinization of the transcriptomes of the Foxl2-depleted cells. However, a quick look at transcriptomic data of Foxl2-depleted ovaries [1] shows that they still ''remember'' that they used to be ovaries.…”

“…Recent articles challenge this view and show that in the ovary active mechanisms are required to maintain the differentiated state. [1,2] The bipotential gonad is made up of four presumptive cell lineages: germ cells (which have an extraembryonic origin) and three types of somatic cells. The somatic component involves the supporting cell precursors, which will give rise to Sertoli cells in the male or granulosa cells in the female, the steroidogenic precursors, which differentiate into Leydig cells (male) and theca cells (female), and finally the connective tissue cells yielding other important structures.…”