Target type: biologicalprocess
The process in which relatively unspecialized cells acquire specialized structural and/or functional features that characterize the mesenchymal cells of the metanephros as it progresses from its formation to the mature state. [GOC:mtg_kidney_jan10]
Metanephric mesenchymal cell differentiation is a complex process that involves the transformation of undifferentiated mesenchymal cells into various specialized cell types that ultimately form the functional nephron, the basic filtration unit of the kidney. This process is tightly regulated by intricate signaling pathways and involves a series of coordinated cellular events.
The metanephric mesenchyme, originating from the intermediate mesoderm, initially consists of undifferentiated cells. These cells express key transcription factors such as Pax2, Wnt4, and Six2, which are essential for maintaining their pluripotent state and responsiveness to inductive signals.
The process begins with the interaction between the metanephric mesenchyme and the ureteric bud, an outgrowth from the Wolffian duct. The ureteric bud, through the expression of factors like GDNF, induces the surrounding mesenchyme to condense and differentiate. This inductive signaling leads to the expression of key transcription factors, including Pax8, Eya1, and Sall1, in the mesenchymal cells.
These transcription factors activate downstream signaling pathways, leading to the formation of a pre-tubular aggregate, the first step in nephron formation. The cells within the aggregate then undergo epithelialization, forming a tubular structure known as the renal vesicle. This vesicle further differentiates into the proximal tubule, loop of Henle, distal tubule, and collecting duct, the various segments of the nephron.
During this differentiation process, the mesenchymal cells undergo a series of morphological and molecular changes. They lose their mesenchymal characteristics and acquire epithelial features, including the expression of epithelial cell markers like E-cadherin and ZO-1. They also establish cell-cell contacts and develop a polarized structure, which is essential for their function in filtration and reabsorption.
The process is further regulated by a complex interplay of growth factors, signaling molecules, and transcription factors. For example, Wnt signaling plays a crucial role in epithelialization and the formation of the renal vesicle. BMP signaling regulates the branching morphogenesis of the ureteric bud and the differentiation of various nephron segments.
Metanephric mesenchymal cell differentiation is a tightly regulated process that is essential for the formation of a functional kidney. Any disruption in this process can lead to congenital kidney diseases, highlighting the importance of understanding the molecular mechanisms underlying this developmental event.'
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Protein | Definition | Taxonomy |
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Protein odd-skipped-related 1 | A protein odd-skipped-related 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8TAX0] | Homo sapiens (human) |
Signal transducer and activator of transcription 1-alpha/beta | A signal transducer and activator of transcription 1 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P42224] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
suramin sodium | suramin sodium : An organic sodium salt that is the hexasodium salt of suramin. It is an FDA approved drug for African sleeping sickness and river blindness. | organic sodium salt | angiogenesis inhibitor; antinematodal drug; antineoplastic agent; apoptosis inhibitor; EC 2.7.11.13 (protein kinase C) inhibitor; GABA antagonist; GABA-gated chloride channel antagonist; purinergic receptor P2 antagonist; ryanodine receptor agonist; trypanocidal drug |
staurosporine | indolocarbazole alkaloid; organic heterooctacyclic compound | apoptosis inducer; bacterial metabolite; EC 2.7.11.13 (protein kinase C) inhibitor; geroprotector | |
epigallocatechin gallate | (-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin. epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis) | flavans; gallate ester; polyphenol | antineoplastic agent; antioxidant; apoptosis inducer; geroprotector; Hsp90 inhibitor; neuroprotective agent; plant metabolite |
nsc 74859 | NSC 74859: inhibits Stat3 binding activity; structure in first source S3I-201 : An amidobenzoic acid obtained by formal condensation of the carboxy group of [(4-methylbenzene-1-sulfonyl)oxy]acetic acid with the amino group of 4-amino-2-hydroxybenzoic acid. | amidobenzoic acid; monohydroxybenzoic acid; tosylate ester | STAT3 inhibitor |
nf 449 | |||
5,15-diphenylporphine | 5,15-diphenylporphine: structure in first source | ||
guttiferone k | guttiferone K: antiproliferative compound of Rheedia calcicola from the Madagascar rain forest; structure in first source |