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XB-ART-58451
Development 2021 Sep 01;14817:. doi: 10.1242/dev.199265.
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Single-minded 2 is required for left-right asymmetric stomach morphogenesis.

Wyatt BH , Amin NM , Bagley K , Wcisel DJ , Dush MK , Yoder JA , Nascone-Yoder NM .


Abstract
The morphogenesis of left-right (LR) asymmetry is a crucial phase of organogenesis. In the digestive tract, the development of anatomical asymmetry is first evident in the leftward curvature of the stomach. To elucidate the molecular events that shape this archetypal laterality, we performed transcriptome analyses of the left versus right sides of the developing stomach in frog embryos. Besides the known LR gene pitx2, the only gene found to be expressed asymmetrically throughout all stages of curvature was single-minded 2 (sim2), a Down Syndrome-related transcription factor and homolog of a Drosophila gene (sim) required for LR asymmetric looping of the fly gut. We demonstrate that sim2 functions downstream of LR patterning cues to regulate key cellular properties and behaviors in the left stomach epithelium that drive asymmetric curvature. Our results reveal unexpected convergent cooption of single-minded genes during the evolution of LR asymmetric morphogenesis, and have implications for dose-dependent roles of laterality factors in non-laterality-related birth defects.

PubMed ID: 34486651
PMC ID: PMC8512893
Article link: Development
Grant support: [+]

Genes referenced: cad pitx2 sim2 sox2
GO keywords: determination of stomach left/right asymmetry
Antibodies: Cdh1 Ab1 Ctnnb1 Ab2 GFP Ab13 Gapdh Ab7 H3f3a Ab9 Itgb1 Ab1 Tuba4b Ab2
Morpholinos: pitx2 MO2 sim2 MO1 sim2 MO2

Disease Ontology terms: Down syndrome
Phenotypes: Xla Wt + SB505124 (Fig. 2. EF) [+]

Article Images: [+] show captions
References [+] :
Aleman, Inhibition of Single Minded 2 gene expression mediates tumor-selective apoptosis and differentiation in human colon cancer cells. 2005, Pubmed