negative regulation of branching involved in ureteric bud morphogenesis
Definition
Target type: biologicalprocess
Any process that decreases the rate, frequency or extent of branching involved in ureteric bud morphogenesis, the process in which the branching structure of the ureteric bud is generated and organized. The ureteric bud is an epithelial tube that grows out from the metanephric duct. The bud elongates and branches to give rise to the ureter and kidney collecting tubules. [GOC:dph, GOC:tb, GOC:yaf]
Negative regulation of branching involved in ureteric bud morphogenesis is a complex process that ensures the proper development of the urinary system. The ureteric bud, an outgrowth from the Wolffian duct, undergoes a series of intricate branching events to form the collecting ducts of the kidney. This branching process is tightly regulated by a variety of signaling pathways and transcription factors, and dysregulation of these pathways can lead to congenital kidney defects. Negative regulation of branching is essential for controlling the size and shape of the collecting duct system and for ensuring that branches form in the correct locations. This negative regulation involves several key mechanisms:
* **Inhibition of branching factors:** Molecules that promote branching, such as GDNF (Glial cell line-derived neurotrophic factor) and its receptor RET, must be tightly regulated to prevent excessive branching. This can occur through the expression of antagonists or inhibitors of these signaling pathways.
* **Activation of branching inhibitors:** Certain molecules, such as Wnt4 and BMP7, specifically inhibit ureteric bud branching. These molecules may act by directly blocking the signaling pathways of branching factors or by inducing the expression of other inhibitory factors.
* **Cellular interactions and mechanical forces:** Interactions between epithelial cells of the ureteric bud and surrounding mesenchymal cells, as well as mechanical forces generated by the growing bud, contribute to the regulation of branching. These forces can influence the expression of branching factors and inhibitors, thereby shaping the branching pattern.
The precise mechanisms of negative regulation of branching are still being unraveled, and it is likely that a combination of these mechanisms, as well as other yet-to-be-identified factors, are involved. Research in this area is critical for understanding the molecular basis of kidney development and for developing potential therapeutic strategies for treating kidney diseases.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Bone morphogenetic protein 4 | A bone morphogenetic protein 4 that is encoded in the genome of human. [PRO:CNA, UniProtKB:P12644] | Homo sapiens (human) |
Compounds (3)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| dorsomorphin | dorsomorphin : A pyrazolopyrimidine that is pyrazolo[1,5-a]pyrimidine which is substituted at positions 3 and 6 by pyridin-4-yl and p-[2-(piperidin-1-yl)ethoxy]phenyl groups, respectively. It is a potent, selective, reversible, and ATP-competitive inhibitor of AMPK (AMP-activated protein kinase, EC 2.7.11.31) and a selective inhibitor of bone morphogenetic protein (BMP) signaling. dorsomorphin: an AMPK inhibitor | aromatic ether; piperidines; pyrazolopyrimidine; pyridines | bone morphogenetic protein receptor antagonist; EC 2.7.11.31 {[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase} inhibitor |
| ldn 193189 | LDN 193189: inhibits bone morphogenetic protein signaling | pyrimidines | |
| ml347 | ML347: an ALK2 inhibitor; structure in first source |