Target type: biologicalprocess
The establishment of the lateral mesoderm with respect to the left and right halves. [GOC:mtg_heart]
The establishment of left-right asymmetry in the lateral mesoderm is a complex process driven by intricate molecular signaling pathways. It involves a cascade of events, beginning with the formation of a signaling center on the left side of the embryo called the "node." The node is characterized by the presence of cilia, hair-like structures that rotate in a clockwise direction, generating a leftward fluid flow. This fluid flow is crucial for the asymmetric activation of downstream signaling pathways.
The leftward flow of fluid activates a signaling pathway involving Nodal, a TGF-beta family member. Nodal, expressed on the left side of the node, is transported by the fluid flow, promoting its accumulation on the left side of the embryo. Nodal activates downstream targets, including Lefty2 and Pitx2, which are crucial for the development of left-sided structures.
Simultaneously, the right side of the embryo expresses a different set of genes, including FGF8 and Shh, which establish a distinct signaling center. This right-sided signaling center inhibits Nodal activity on the right side of the embryo, contributing to the establishment of left-right asymmetry.
The asymmetric distribution of Nodal signaling creates a molecular gradient, with high concentrations of Nodal on the left side and lower concentrations on the right. This gradient influences the development of various organs, such as the heart, lungs, and gut, ensuring their correct positioning and function. For instance, the heart develops on the left side of the body, while the liver develops on the right.
The determination of left-right asymmetry in the lateral mesoderm is therefore a tightly regulated process involving intricate molecular signaling pathways and physical cues. This process is essential for the proper development and function of various organs in the body.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Smoothened homolog | A protein smoothened that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q99835] | Homo sapiens (human) |
| Sonic hedgehog protein | A sonic hedgehog protein that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15465] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| jervine | jervine: teratogen from Veratrum grandiflorum; RN given refers to parent cpd(3beta,23beta)-isomer; structure | piperidines | |
| 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 | |
| robotnikinin | robotnikinin: binds sonic hedgehog protein to block its signaling pathway; structure in first source | ||
| 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 |