Fons Juan M, Ocaña Oscar H, Nieto M Angela
Instituto de Neurociencias (CSIC-UMH), Avda. Ramón y Cajal s/n, Sant Joan d'Alacant, Spain.
Development. 2025 Aug 15;152(16). doi: 10.1242/dev.204848.
The pronephros is the first renal structure in the embryo, arising by mesenchymal-to-epithelial transition of the intermediate mesoderm, where Pax2 induces epithelialization and differentiation of this mesenchyme. Here, we show in chick embryos that Snail1 is sufficient to keep the intermediate mesoderm in an undifferentiated state by directly repressing Pax2 transcription. Reciprocally, Pax2 is sufficient and necessary to induce mesenchymal-to-epithelial transition by directly repressing Snail1 expression. We also show that BMP7 acts as an epithelialization signal by downregulating Snail1 and upregulating Pax2 expression. This, together with the Snail1/Pax2 reciprocal repression, establishes a regulatory loop within the bi-stability domain, a dynamic region of the anteroposterior axis where opposing retinoic acid/fibroblast growth factor gradients converge, and which has been found to regulate differentiation of the neural tube and somites. In conclusion, we show that the antagonism between Snail1 and Pax2 determines the epithelial/mesenchymal state during the differentiation of the intermediate mesoderm and propose that the bi-stability domain extends to the intermediate mesoderm, synchronizing the differentiation of all tissues aligned along the mediolateral embryonic axis.
原肾是胚胎中的第一个肾脏结构，由中间中胚层的间充质上皮转化产生，其中Pax2诱导该间充质的上皮化和分化。在此，我们在鸡胚中表明，Snail1通过直接抑制Pax2转录足以使中间中胚层保持未分化状态。相反，Pax2通过直接抑制Snail1表达来诱导间充质上皮转化，这是充分且必要的。我们还表明，BMP7通过下调Snail1和上调Pax2表达来充当上皮化信号。这与Snail1/Pax2相互抑制一起，在双稳态域内建立了一个调节环，双稳态域是前后轴的一个动态区域，在该区域中，相反的视黄酸/成纤维细胞生长因子梯度汇聚，并且已发现该区域调节神经管和体节的分化。总之，我们表明Snail1和Pax2之间的拮抗作用决定了中间中胚层分化过程中的上皮/间充质状态，并提出双稳态域延伸至中间中胚层，使沿胚胎中外侧轴排列的所有组织的分化同步。
