Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

How do vertebrate epithelial appendages form from the flat epithelia? Following the formation of feather placodes, the previously radially symmetrical primordia become anterior-posterior (A-P) asymmetrical and develop a proximo-distal (P-D) axis. Analysis of the molecular heterogeneity revealed a surprising parallel of molecular profiles in the A-P feather buds and the ventral-dorsal (V-D) Drosophila appendage imaginal discs. The functional significance was tested with an in vitro feather reconstitution model. Wnt-7a expression initiated all over the feather tract epithelium, intensifying as it became restricted first to the primordia domain, then to an accentuated ring pattern within the primordia border, and finally to the posterior bud. In contrast, sonic hedgehog expression was induced later as a dot within the primordia. RCAS was used to overexpress Wnt-7a in reconstituted feather explants derived from stage 29 dorsal skin to further test its function in feather formation. Control skin formed normal elongated, slender buds with A-P orientation, but Wnt-7a overexpression led to plateau-like skin appendages lacking an A-P axis. Feathers in the Wnt-7a overexpressing skin also had inhibited elongation of the P-D axes. This was not due to a lack of cell proliferation, which actually was increased although randomly distributed. While morphogenesis was perturbed, differentiation proceeded as indicated by the formation of barb ridges. Wnt-7a buds have reduced expression of anterior (Tenascin) bud markers. Middle (Notch-1) and posterior bud markers including Delta-1 and Serrate-1 were diffusely expressed. The results showed that ectopic Wnt-7a expression enhanced properties characteristic of the middle and posterior feather buds and suggest that P-D elongation of vertebrate skin appendages requires balanced interactions between the anterior and posterior buds.
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PMID:Wnt-7a in feather morphogenesis: involvement of anterior-posterior asymmetry and proximal-distal elongation demonstrated with an in vitro reconstitution model. 1033 70

Lung morphogenesis is stereotypic, both for lobation and for the first several generations of airways, implying mechanistic control by a well conserved, genetically hardwired developmental program. This program is not only directed by transcriptional factors and peptide growth factor signaling, but also co-opts and is modulated by physical forces. Peptide growth factors signal within repeating epithelial-mesenchymal temporospatial patterns that constitute morphogenetic centers, automatically directing millions of repetitive events during both stereotypic branching and nonstereotypic branching as well as alveolar surface expansion phases of lung development. Transduction of peptide growth factor signaling within these centers is finely regulated at multiple levels. These may include ligand expression, proteolytic activation of latent ligand, ligand bioavailability, ligand binding proteins and receptor affinity and presentation, receptor complex assembly and kinase activation, phosphorylation and activation of adapter and messenger protein complexes as well as downstream events and cross-talk both inside and outside the nucleus. Herein we review the critical Sonic Hedgehog, Fibroblast Growth Factor, Bone Morphogenetic Protein, Vascular Endothelial Growth Factor and Transforming Growth Factorbeta signaling pathways and propose how they may be functionally coordinated within compound, highly regulated morphogenetic gradients that drive first stereotypic and then non-stereotypic, automatically repetitive, symmetrical as well as asymmetrical branching events in the lung.
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PMID:Growth factor signaling in lung morphogenetic centers: automaticity, stereotypy and symmetry. 1281 6

Avian left-right (L/R) axis determination involves the establishment of asymmetric gene expression in Hensen's node, resulting in two discrete signalling pathways on the left and right sides of the embryo. The extracellular signalling molecule Sonic Hedgehog (SHH) is known to be an important left-side determinant. Transcription of Shh is initially bilateral in Hensen's node (stage 4), but is restricted to the left side by stage 5. The Gli genes (Gli1, Gli2 and Gli3) are the main transcriptional mediators of the Hedgehog pathway in vertebrates. GLI1 and GLI2 are primarily transcriptional activators of Hedgehog target genes, while GLI3 is primarily a transcriptional repressor of Hedgehog targets. In order to gain insight into the mechanisms of asymmetrical Hedgehog signal transduction in the node, we have analysed the expression patterns of the Gli genes in Hensen's node from stage 4 to stage 8. Here, we reveal that the Gli genes are asymmetrically expressed in Hensen's node: Gli1 and Gli2, are expressed on the left side, while Gli3 is expressed on the right side.
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PMID:Asymmetric expression of Gli transcription factors in Hensen's node. 1574 82

Timing of embryonic development is precisely controlled, but the mechanisms underlying biological timers are still unclear. Here, a validated model for timing under control of Sonic Hedgehog is revisited and generalized to an arbitrary number of genes. The developmental dynamics where a temporal sequence of gene expression recapitulates a steady-state spatial pattern can be realized through a simple network close to criticality, controlled by the duration of exposure to a morphogen. Criticality simultaneously accounts for many observed biological properties, such as timing, multistability, and canalization of genetic expression. This process can be parsimoniously generalized in many dimensions with a minimum number of genes, all repressing each other with asymmetrical strengths, which also explains sequential activation of different fates. Separation of timescales allows for a simple analytical interpretation. Finally, it is shown that even in the presence of noise, coupling between cells preserves criticality and robust patterning. The model offers a simple theoretical framework for the study of emergent developmental timers.
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PMID:Critical Timing without a Timer for Embryonic Development. 2648 64

Horseshoe kidneys are a common, yet enigmatic, renal malformation. This review critically appraised the literature surrounding the embryology, etiology and clinical anatomy of horseshoe kidneys. The systematic literature search produced 104 articles, and 56 primary and further secondary references. There were several etiological theories regarding horseshoe kidneys. The established view was that during ascent, the kidneys come into close apposition as they pass through an arterial fork. Another possible mechanism related to lateral flexion of the trunk or rotation of the caudal embryo; the association of asymmetrical horseshoe kidneys with a number of vertebral conditions supported this hypothesis. More recent animal models implicated the notochord and sonic hedgehog signaling. Furthermore, it has been suggested that the isthmus may be the result of ectopic mesenchymal tissue. Surgical anatomy of the horseshoe kidney is complex, due to variability in location, orientation and blood supply. Both arterial and venous anatomy is highly variable. This raised the question of whether anomalous blood supply is the cause or result of abnormal renal position. In the majority of cases, the isthmus contained functional renal parenchyma. In over 90% of cases, fusion between the kidneys occurred at the lower pole. Despite commonly being quoted as 'held back by the inferior mesenteric artery' at L3, in reality the isthmus was only found immediately inferior to this in 40% of cases.
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PMID:The horseshoe kidney: Surgical anatomy and embryology. 2732 57

In recent years, the hypothesis of the presence of tumor-initiating cancer stem cells (CSCs) has received a considerable support. This model suggested the existence of CSCs which, thanks to their self-renewal properties, are able to drive the expansion and the maintenance of malignant cell populations with invasive and metastatic potential in cancer. Increasing evidence showed the ability of such cells to acquire self-renewal, multipotency, angiogenic potential, immune evasion, symmetrical and asymmetrical divisions which, along with the presence of several DNA repair mechanisms, further enhance their oncogenic potential making them highly resistant to common anticancer treatments. The main signaling pathways involved in the homeostasis of colorectal (CRC) stem cells are the Wnt, Notch, Sonic Hedgehog, and Bone Morfogenic Protein (BMP) pathways, which are mostly responsible for all the features that have been widely referred to stem cells. The same pathways have been identified in colorectal cancer stem cells (CRCSCs), conferring a more aggressive phenotype compared to non-stem CRC cells. Recently, several evidences suggested that non-coding RNAs (ncRNAs) may play a crucial role in the regulation of different biological mechanisms in CRC, by modulating the expression of critical stem cell transcription factors that have been found active in CSCs. In this chapter, we will discuss the involvement of ncRNAs, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), in stemness acquisition and maintenance by CRCSCs, through the regulation of pathways modulating the CSC phenotype and growth, carcinogenesis, differentiation, and epithelial to mesenchymal transition (EMT).
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PMID:Non-coding RNAs Functioning in Colorectal Cancer Stem Cells. 2757 96