PITX2 controls asymmetric gonadal development in both sexes of the chick and can rescue the degeneration of the right ovary
PITX2 controls asymmetric gonadal development in both sexes of the chick and can rescue the degeneration of the right ovary
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DOI：
10.1242/dev.010249
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发表时间：
2007-12-01
期刊：
影响因子：
4.6
通讯作者：
Lovell-Badge, Robin
中科院分区：
文献类型：
--
作者：
Guioli, Silvana;Lovell-Badge, Robin
性腺出现在每个中肾的腹内侧表面。在大多数鸟类中，雌性性腺发育是不寻常的，因为只有左侧卵巢具有功能，而右侧卵巢在胚胎发生过程中退化。雄性发育出一对功能相同的睾丸。我们发现，在不同性别（生殖脊）阶段，雏鸡性腺已经具有明显的两性形态和分子左右（L-R）特征，并且这些特征持续存在，在性别决定和分化过程中变得更加复杂，但对睾丸分化没有影响。我们发现这些 L-R 差异取决于控制心脏和肠道等器官位置的 L-R 不对称通路。此外，其关键决定因素 Pitx2 的表达不对称，因此从发育之初起，它仅在两性的左侧性腺中发现。在性腺发生之前和期间，右侧 Pitx2 的错误表达足以将右侧性腺转变为左侧性腺。在 ZW 胚胎中，这种转变挽救了右侧卵巢的退化命运，允许含有减数分裂生殖细胞的左侧皮质分化。因此，女性体内存在一种机制，积极促进 Pitx2 引发的潜在 L-R 不对称性和右侧性腺的退化，而男性体内存在一种机制，允许它被忽略或覆盖。
The gonads arise on the ventromedial surface of each mesonephros. In most birds, female gonadal development is unusual in that only the left ovary becomes functional, whereas that on the right degenerates during embryogenesis. Males develop a pair of equally functional testes. We show that the chick gonads already have distinct morphological and molecular left-right (L-R) characteristics in both sexes at indifferent (genital ridge) stages and that these persist, becoming more elaborate during sex determination and differentiation, but have no consequences for testis differentiation. We find that these L-R differences depend on the L-R asymmetry pathway that controls the situs of organs such as the heart and gut. Moreover, a key determinant of this, Pitx2, is expressed asymmetrically, such that it is found only in the left gonad in both sexes from the start of their development. Misexpression of Pitx2 on the right side before and during gonadogenesis is sufficient to transform the right gonad into a left-like gonad. In ZW embryos, this transformation rescues the degenerative fate of the right ovary, allowing for the differentiation of left-like cortex containing meiotic germ cells. There is therefore a mechanism in females that actively promotes the underlying L-R asymmetry initiated by Pitx2 and the degeneration of the right gonad, and a mechanism in males that allows it to be ignored or overridden.