mesenchymal to epithelial transition involved in metanephric renal vesicle formation
Definition
Target type: biologicalprocess
A 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 metanephric renal vesicle. [GOC:mtg_kidney_jan10]
Metanephric renal vesicle formation involves a complex process of mesenchymal to epithelial transition (MET). This transition is critical for the development of the nephron, the functional unit of the kidney. Here's a detailed description:
1. **Mesenchymal Cells:** The process begins with mesenchymal cells, undifferentiated cells that are derived from the metanephric mesenchyme. These cells have a loose, fibroblast-like morphology and express specific markers such as Pax2 and Wnt4.
2. **Induction by the Ureteric Bud:** The ureteric bud, an outgrowth from the Wolffian duct, interacts with the metanephric mesenchyme, triggering the MET process. This interaction is mediated by reciprocal signaling pathways, including GDNF (glial cell line-derived neurotrophic factor) from the mesenchyme and RET (receptor tyrosine kinase) from the ureteric bud.
3. **Epithelial Commitment and Cell Aggregation:** The inductive signals from the ureteric bud initiate a cascade of events that cause mesenchymal cells to commit to an epithelial fate. They begin to express epithelial markers like E-cadherin and ZO-1, and their morphology changes from fibroblast-like to rounded, epithelial-like cells. These cells then aggregate around the tips of the ureteric bud branches, forming epithelial spheres known as renal vesicles.
4. **Polarization and Lumen Formation:** As the renal vesicles form, the epithelial cells undergo polarization. The apical surfaces of the cells face the lumen of the vesicle, while the basolateral surfaces face the surrounding mesenchyme. This polarization is crucial for the formation of a functional lumen within the vesicle.
5. **Differentiation and Nephron Development:** The renal vesicles further differentiate into various segments of the nephron, including the glomerulus, proximal tubule, loop of Henle, and distal tubule. This differentiation involves the expression of specific genes and the formation of specialized cell types within the nephron.
The mesenchymal to epithelial transition during metanephric renal vesicle formation is a tightly regulated process involving complex signaling pathways, transcription factors, and cell-cell interactions. It is essential for the proper development of the kidney and its ability to filter blood and produce urine.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Smoothened homolog | A protein smoothened that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q99835] | Homo sapiens (human) |
Compounds (15)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| cyclopamine | piperidines | glioma-associated oncogene inhibitor | |
| pd 173955 | PD 173955: inhibits src family-selective tyrosine kinase; structure in first source | aryl sulfide; dichlorobenzene; methyl sulfide; pyridopyrimidine | tyrosine kinase inhibitor |
| purmorphamine | purmorphamine : A member of the class of purines that is purine substituted at C-2 by a 1-naphthyloxy group, at C-4 by a 4-morpholinophenylamino group, and at N-9 by a cyclohexyl group. purmorphamine: structure in first source | aromatic ether; morpholines; purines; secondary amino compound | osteogenesis regulator; SMO receptor agonist |
| cur 61414 | CUR 61414: inhibits the hedehog signaling pathway; structure in first source | ||
| abt 869 | aromatic amine; indazoles; phenylureas | angiogenesis inhibitor; antineoplastic agent; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor | |
| lde225 | sonidegib : A member of the classo of biphenyls that is the amide obtained by formal condensation of the carboxy group of 2-methyl-4'-(trifluoromethoxy)[1,1'-biphenyl]-3-carboxylic acid with the amino group of 6-(2,6-dimethylmorpholin-4-yl)pyridin-3-amine. Used (as its phosphate salt) for treatment of locally advanced basal cell carcinoma. sonidegib: specific Smoothened/Smo antagonist | aminopyridine; aromatic ether; benzamides; biphenyls; morpholines; organofluorine compound; tertiary amino compound | antineoplastic agent; Hedgehog signaling pathway inhibitor; SMO receptor antagonist |
| gdc 0449 | HhAntag691: inhibits the hedgehog pathway and ABC transporters; has antineoplastic activity | benzamides; monochlorobenzenes; pyridines; sulfone | antineoplastic agent; Hedgehog signaling pathway inhibitor; SMO receptor antagonist; teratogenic agent |
| N-[[3-fluoro-4-[[2-(1-methyl-4-imidazolyl)-7-thieno[3,2-b]pyridinyl]oxy]anilino]-sulfanylidenemethyl]-2-phenylacetamide | thioureas | ||
| ipi-926 | IPI-926: a semisynthetic derivative of cyclopamine that is a smoothened inhibitor with antineoplastic activity; structure in first source | piperidines | |
| gsk 1363089 | GSK 1363089: a multikinase inhibitor that acts on Met, RON, Axl, and VEGFR; structure in first source | aromatic ether | |
| tak-441 | TAK-441: structure in first source | ||
| ly2940680 | |||
| 3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-(6-(4-(4-ethylpiperazin-1-yl)-phenylamino)pyrimidin-4-yl)-1-methylurea | BGJ-398 : A member of the class of phenylureas that is urea in which a hydrogen attached to one of the nitrogens is replaced by a 2,6-dichloro-3,5-dimethoxyphenyl group, while the hydrogens attached to the other nitrogen are replaced by a methyl group and a 6-{[4-(4-ethylpiperazin-1-yl)phenyl]amino}pyrimidin-4-yl group. It is a potent and selective fibroblast growth factor receptor inhibitor. infigratinib: structure in first source | aminopyrimidine; dichlorobenzene; N-alkylpiperazine; N-arylpiperazine; phenylureas | antineoplastic agent; fibroblast growth factor receptor antagonist |
| cep-32496 | agerafenib: inhibitor of RAF family kinases; structure in first source | ||
| pf-5274857 | 1-(4-(5'-chloro-3,5-dimethyl-2,4'-bipyridin-2'-yl)piperazin-1-yl)-3-(methylsulfonyl)propan-1-one: a potent and selective Smoothened antagonist that penetrates the blood-brain barrier; structure in first source |