Disease relevance of Foxl2

• Mice homozygous mutant for Foxl2 display craniofacial malformations and female infertility [1].
• The polled intersex syndrome (PIS) in goats, which shares some features with blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) in humans, exemplifies such syndromes [2].
• The retina of the pearl mutant mouse, C57BL/6J pe/pe, exhibits reduced light sensitivity in the dark-adapted condition (Balkema and Pinto, J Neurophysiol 48:968, 1982) [3].

High impact information on Foxl2

• Analysis of pituitary development in the Small eye and Pax6 -/- mouse mutants reveals that the dorsoventral axis of the pituitary gland becomes ventralized, with dorsal extension of the transcriptional determinants of ventral cell types, particularly PFrk [4].
• We find that mouse XX gonads lacking the forkhead transcription factor Foxl2 form meiotic prophase oocytes, but then activate the genetic program for somatic testis determination [5].
• The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance [6].
• Expression of Foxl2 was detected in early ovaries of all three species around the time of sex determination and was associated with both somatic and germ cell populations in mice [7].
• Analysis of resulting Sox9(-/-) XY gonads up to E15.5 reveals immediate, complete sex reversal, as shown by expression of the early ovary-specific markers Wnt4 and Foxl2 and by lack of testis cord and Leydig cell formation [8].

Biological context of Foxl2

• This species-specific difference could explain the phenotype discrepancy observed between XX goat PIS(-/-) and XX mouse Foxl2(-/-) [9].
• In mouse, we have previously suggested the existence of two mRNA isoforms of Foxl2 that result from an alternative polyadenylation [10].
• Studies would prominently include gene expression profiling of developmental-specific pathways in nascent ovaries with controlled levels of Foxl2 and interacting proteins, or with defined changes in the X chromosome [11].
• Retinal projections to the pretectal and terminal accessory optic nuclei were studied in normal wild-type mice and mutant mice with abnormal optokinetic nystagmus (OKN, Mangini, Vanable, Williams, and Pinto: J. Comp. Neurol. 241:191-209, '85) [12].

Anatomical context of Foxl2

• Foxl2OS displays a pattern of expression very similar to that of Foxl2 in the gonads during development and at the adult age [10].
• The time of maximal occurrence of pyknotic nuclei in the retinal ganglion cell layer of postnatal pearl mutant mice is earlier than that in normal mice (Linden and Pinto 1985) [13].
• Penetration of the salivary glands of Rhodnius domesticus Neiva & Pinto, 1923 (Hemiptera: Reduviidae) by Trypanosoma rangeli Tejera, 1920 (Protozoa: Kinetoplastida) [14].

Other interactions of Foxl2

• Identification of the functional roles of several novel regulatory elements such as Figalpha, Foxl2, follistatin, and Wnt4 reveals the complexity of early ovarian organization [15].

References