negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis

Definition

Target type: biologicalprocess

Any process that decreases the rate, frequency or extent of the transition where a mesenchymal cell establishes apical/basolateral polarity,forms intercellular adhesive junctions, synthesizes basement membrane components and becomes an epithelial cell that will contribute to the shaping of the metanephros. [GOC:dph, GOC:yaf]

Negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis is a crucial biological process during kidney development. Metanephros, the permanent kidney in mammals, arises from reciprocal interactions between two distinct tissues: the metanephric mesenchyme and the ureteric bud. The metanephric mesenchyme, derived from the intermediate mesoderm, is composed of undifferentiated mesenchymal cells. These mesenchymal cells undergo epithelialization, transforming into epithelial cells that form the nephrons, the functional units of the kidney. This transition, termed mesenchymal to epithelial transition (MET), is tightly regulated by various signaling pathways and transcription factors. Negative regulation of MET ensures that this process occurs in a controlled and spatially restricted manner, preventing uncontrolled epithelialization and ensuring proper kidney formation. The precise mechanisms underlying this negative regulation are complex and involve a interplay of several factors:

- **BMP signaling:** Bone morphogenetic proteins (BMPs) are secreted signaling molecules known to inhibit MET in the metanephric mesenchyme. BMP signaling promotes mesenchymal cell survival and prevents premature differentiation into epithelial cells.
- **Wnt signaling:** Wnt signaling pathways, particularly Wnt4, are also involved in negative regulation of MET. Wnt4 acts as a repressor of epithelial differentiation, maintaining mesenchymal cell fate and preventing premature epithelialization.
- **Slit-Robo signaling:** The Slit-Robo signaling pathway is another important regulator of MET. Slit proteins, secreted from the ureteric bud, bind to Robo receptors on mesenchymal cells, repressing MET and promoting mesenchymal cell migration towards the ureteric bud.
- **Transcription factors:** Several transcription factors are involved in regulating MET, including Pax2, Six2, and Osr1. These factors maintain mesenchymal cell fate and suppress epithelialization, contributing to the negative regulation of MET.

Overall, negative regulation of MET is a critical process for proper metanephros morphogenesis. It ensures that the metanephric mesenchyme remains in a mesenchymal state until appropriate signals from the ureteric bud trigger MET and nephron formation. This fine-tuned regulation ensures the correct timing and spatial arrangement of epithelial cells, leading to the development of a functional kidney.'
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Proteins (2)

Compounds (12)