Fig 11

Fig 11 Summary of genetic analysis and working hypotheses on mechanisms of Bmp15 action in zebrafish.

(A) Zebrafish folliculogenesis and phenotypic defects of single (bmp15-/- and gdf9-/-), double (bmp15-/-;inha-/-) and triple (bmp15-/-;inha-/-;inhbaa-/-) mutants. The loss of gdf9 and Bmp15 caused a complete arrest of follicle development at PG and PV stage, respectively. The bmp15-/- follicles showed normal formation of cortical alveoli but no yolk mass in the oocyte, followed by sex reversal to males. Double mutation with inha (bmp15-/-;inha-/-) prevented sex reversal and partially rescued the vitellogenic growth with yolk mass to MV stage. Further knockout of inhbaa in the triple mutant (bmp15-/-;inha-/-;inhbaa-/-) resulted in the loss of yolk granules again but allowed the oocytes to grow to EV size. (B) Roles of Gdf9 and Bmp15 in controlling early follicle development in zebrafish. Gdf9 is primarily involved in controlling PG-PV transition or follicle activation as a determinant; in contrast, Bmp15 is a key factor controlling PV-EV transition, the subsequent stage that marks the start of vitellogenic growth. Bmp15 is also involved in promoting PG-PV transition as an accelerator. EPN, early perinucleolar; LPN, late perinucleolar. (C) Actions and interactions of Bmp15 from the oocyte, activin/inhibin from the follicle cells and FSH from the pituitary in controlling aromatase (cyp19a1a) expression and Vtg biosynthesis as well as uptake. (D) Potential roles for Bmp15 and Gdf9 in regulating formation of cortical alveoli and yolk granules. Gdf9 may stimulate the biogenesis of cortical alveoli in the oocyte, while Bmp15 may play an antagonistic role in this regard while promoting yolk formation.