Benner Lars Kristian, Prothro Katherine Perkins, McJunkin Katherine
NIDDK Intramural Research Program, National Institutes of Health, Bethesda, MD 20892.
NIDDK Intramural Research Program, National Institutes of Health, Bethesda, MD 20892
G3 (Bethesda). 2019 Mar 7;9(3):901-909. doi: 10.1534/g3.118.200863.
The germline sex determination pathway in determines whether germ cells develop as oocytes or sperm, with no previously known effect on viability. The family of microRNAs are expressed in the germline and embryo and are essential for both viability and normal hermaphroditic sex determination, preventing aberrant male gene expression in XX hermaphrodite embryos. Here we show that combining feminizing mutations with partial loss of function of the family results in enhanced penetrance embryonic lethality that preferentially kills XO animals. This lethal phenotype is due to altered signaling through the germline sex determination pathway, and maternal germline feminization is sufficient to induce enhanced lethality. These findings reveal a surprising pleiotropy of sperm-fate promoting pathways on organismal viability. Overall, our results demonstrate an unexpectedly strong link between sex determination and embryonic viability, and suggest that in wild type animals, family members buffer against misregulation of pathways outside the sex determination program, allowing for clean sex reversal rather than deleterious effects of perturbing sex determination genes.
[物种名称]中的生殖系性别决定途径决定生殖细胞发育为卵母细胞还是精子，此前未知其对生存能力有影响。微小RNA家族在[物种名称]的生殖系和胚胎中表达，对生存能力和正常雌雄同体性别决定至关重要，可防止XX雌雄同体胚胎中出现异常的雄性基因表达。在此，我们表明，将雌性化突变与微小RNA家族功能部分丧失相结合，会导致胚胎致死率的外显率增加，优先杀死XO动物。这种致死表型是由于生殖系性别决定途径的信号传导改变所致，母本生殖系雌性化足以诱导增强的致死率。这些发现揭示了精子命运促进途径对生物体生存能力的惊人多效性。总体而言，我们的结果证明了性别决定与胚胎生存能力之间存在出乎意料的紧密联系，并表明在野生型动物中，微小RNA家族成员可缓冲性别决定程序之外途径的失调，从而实现清晰的性别逆转，而非干扰性别决定基因带来的有害影响。
