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Dev Cell 2019 Dec 16;516:675-683.e4. doi: 10.1016/j.devcel.2019.11.002.
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Isl1 Regulation of Nkx2.1 in the Early Foregut Epithelium Is Required for Trachea-Esophageal Separation and Lung Lobation.

Kim E , Jiang M , Huang H , Zhang Y , Tjota N , Gao X , Robert J , Gilmore N , Gan L , Que J .

The esophagus and trachea arise from the dorsal and ventral aspects of the anterior foregut, respectively. Abnormal trachea-esophageal separation leads to the common birth defect esophageal atresia with or without trachea-esophageal fistula (EA/TEF). Yet the underlying cellular mechanisms remain unknown. Here, we combine Xenopus and mouse genetic models to identify that the transcription factor Isl1 orchestrates trachea-esophageal separation through modulating a specific epithelial progenitor cell population (midline epithelial cells [MECs], Isl1+ Nkx2.1+ Sox2+) located at the dorsal-ventral boundary of the foregut. Lineage tracing experiments show that MECs contribute to both tracheal and esophageal epithelium, and Isl1 is required for Nkx2.1 transcription in MECs. Deletion of the chromosomal region spanning the ISL1 gene has been found in patients with abnormal trachea-esophageal separation. Our studies thus provide definitive evidence that ISL1 is a critical player in the process of foregut morphogenesis, acting in a small progenitor population of boundary cells.

PubMed ID: 31813798
PMC ID: PMC6919560
Article link: Dev Cell
Grant support: [+]

Species referenced: Xenopus
Genes referenced: isl1 shh sox2 sox9 tp63
GO keywords: foregut morphogenesis
Morpholinos: Isl1 MO Mrpl24 MO Ovol2 MO Sall1 MO

Article Images: [+] show captions
References [+] :
Ahlgren, Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. 1997, Pubmed