Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes

Yashiro, Kenta; Saijoh, Yukio; Sakuma, Rui; Tada, Masatomo; Tomita, Naohiro; Amano, Kenji; Matsuda, Youichi; Monden, Morito; Okada, Shintaro; Hamada, Hiroshi

doi:10.1046/j.1365-2443.2000.00329.x

Cited by 46 publications

(49 citation statements)

References 46 publications

(69 reference statements)

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“…Lefty locus contains two genes with the same transcriptional orientation in human, mice, and zebrafish. Human Lefty1 is identical to mice LeftyB and Lefty2 is identical to human LeftyA (10)(11)(12)(13). LeftyB has 96% sequence identity with LeftyA and these two proteins differ only in 16 amino acids.…”

Section: Tgf Beta Family and Pathway Signalingmentioning

confidence: 99%

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TGF-beta Family Signaling in Embryonic Stem Cells

Park¹

2011

Int J Stem Cells

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TGF-beta Family Signaling in Embryonic Stem Cells Kyung-Soon Park Department of Biomedical Science, College of Life Science, CHA University, Seongnam, KoreaLigands of transforming growth factor beta (TGF-β) family members have been implicated in the development and patho-physiological process of various organs. Embryonic stem cells (ESCs) are characterized by their ability to proliferate indefinitely and differentiated into all three germ layer cells, which are termed as pluripotency and self-renewal, respectively. For successful therapeutic application of ESCs, it is essential to understand the mechanisms underlying self-renewal and pluripotency, which involve complex networks among key factors including transcription factors, epigenetic control, microRNAs and signaling pathways. In this review, we discuss recent progress on the function of TGF beta family ligands and their canonical SMAD signaling in the maintenance of ESC's identity.

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Section: Tgf Beta Family and Pathway Signalingmentioning

confidence: 99%

“…LeftyB has 96% sequence identity with LeftyA and these two proteins differ only in 16 amino acids. However, LeftyB has only 82% sequence identity with Lefty1, which suggests that Lefty proteins has been evolved independently in mouse and humans after the duplication of a single Lefty gene (10).…”

Section: Tgf Beta Family and Pathway Signalingmentioning

confidence: 99%

TGF-beta Family Signaling in Embryonic Stem Cells

Park¹

2011

Int J Stem Cells

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“…LEFTY1 belongs to the family of LEFTY genes involved in the left-right determination 65 . Yashiro et al 65 study the LEFTY pair for human cases in colon.…”

Section: Dicationmentioning

confidence: 99%

“…Yashiro et al 65 study the LEFTY pair for human cases in colon. They show that the LEFTY1 is highly expressed in colorectal cancer as well as normal colon and point that it is not easy to correlate the two phenomena.…”

Section: Dicationmentioning

confidence: 99%

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Revealing ETC-1922159 Affected Unknown 3rd order WNT10B-X-X Combinations, in Silico

Sinha¹

2017

Preprint

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WNT10B belongs to the family of WNT proteins that are implicated in a range of phenomena that are affected by the Wnt signaling pathway. Recent studies have shown that WNT10B plays a role in colorectal cancer. WNTs have been found to directly affect the stemness of the tumor cells via regulation of ASCL2. Switching off the ASCL2 literally blocks the stemness process of the tumor cells and vice versa. Furthermore, recent findings suggest BVES to be highly suppressed in malignancies and in vitro deletions of BVES show higher Wnt signaling activity to induce stemness. WNT10B was found to be highly expressed in such cases. Often, in biology, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be affecting the pathway under certain conditions. For example, WNT10B-ASCL2 is one such 2 nd order combination whose relation needs to be tested under the influence of recently developed porcupine-WNT inhibitor ETC-1922159. The inhibitor is known to suppress PORCN (porcupine) and thus inhibit a range of oncogenes known to be directly or indirectly affected by the Wnts. In a recent unpublished work in bioRxiv, Sinha 1 , we had the opportunity to rank these unknown biological hypotheses for down regulated genes at 2 nd order level after the drug was administered. The in silico observations showed that the combination of WNT10B-ASCL2 was assigned a relatively lower rank, thus validating the pipeline's efficacy with the confirmed wet lab experiment that indicate that both WNT10B and ASCL2 were down regulated after treatment in cancer cells. Here, we take one step further by in silico analysis of the 3 rd order combinations of WNT10B-X-X (X can be known or unknown factor), from a range of 100 randomly picked down regulated genes after ETC-1922159 treatment. The pipeline uses the density based HSIC (Hilbert Schmidt Information Criterion) sensitivity index with an rbf (radial basis function) kernel, which is known to be highly effective in sensitivity analysis. Various unknown/unexplored/untested 3 rd order biological hypotheses emerge some of which are confirmed in wet lab, while others need to be tested. The potential of such ranking is indispensable in the current era of search in a vast combinatorial forest. KEYWORDS -WNT pathway; porcupine inhibitor ETC-1922159; sensitivity analysis; colorectal cancer; unknown biological hypotheses; combinatorial search space; support vector ranking Conference, from 6-11 August 2017, held Significance WNT10B belongs to the family of WNT proteins that are implicated in a range of phenomena that are affected by the Wnt signaling pathway. Recent studies have shown that WNT10B plays a role in colorectal cancer. Often, we are faced with the problem of exploring relevant unknown biological hypotheses in the form of myriads of combination of factors that might be involved in the pathway. The current work reveals at in silico level, the 3rd order WNT10B associated combinations that might be affected by the admin...

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Of mice and men: Dissecting the genetic pathway that controls left-right asymmetry in mice and humans

Schneider

Brueckner

2000

Am. J. Med. Genet.

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The increasing ability to manipulate the mouse genetically has created a model system that is both accessible and an accurate mirror of human development. A combination of analysis of existing spontaneous mouse mutations and creation of targeted mutations has identified at least z24 genes involved in the specification of mouse left-right asymmetry. These genes function in a carefully orchestrated manner first to create asymmetry at the node, then to signal it to the immediately surrounding cells via the node monocilia, and finally to amplify the initial asymmetry and propagate it to the developing organs. Defects at different steps in this pathway result in differences in the final phenotype. Human homologues exist for most of the mouse left-right determining genes. Notably, when human mutations in these genes have been identified in patients with defects of laterality determination, the human phenotype correlates very closely with the corresponding mouse phenotype.

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Distinct transcriptional regulation and phylogenetic divergence of human LEFTY genes

Abstract: Background: Mouse lefty1 and lefty2 genes are expressed on the left side of developing embryos and are required for left-right determination. Here we have studied expression and transcriptional regulatory mechanisms of human LEFTY genes.

Cited by 46 publications

References 46 publications

TGF-beta Family Signaling in Embryonic Stem Cells

TGF-beta Family Signaling in Embryonic Stem Cells

Revealing ETC-1922159 Affected Unknown 3<em><sup>rd</sup></em> order WNT10B-X-X Combinations, in Silico

Of mice and men: Dissecting the genetic pathway that controls left-right asymmetry in mice and humans

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