| First Author | Lewis AE | Year | 2022 |
| Journal | Cell Rep | Volume | 38 |
| Issue | 11 | Pages | 110510 |
| PubMed ID | 35294885 | Mgi Jnum | J:324831 |
| Mgi Id | MGI:7281979 | Doi | 10.1016/j.celrep.2022.110510 |
| Citation | Lewis AE, et al. (2022) Tracheal separation is driven by NKX2-1-mediated repression of Efnb2 and regulation of endodermal cell sorting. Cell Rep 38(11):110510 |
| abstractText | The mechanisms coupling fate specification of distinct tissues to their physical separation remain to be understood. The trachea and esophagus differentiate from a single tube of definitive endoderm, requiring the transcription factors SOX2 and NKX2-1, but how the dorsoventral site of tissue separation is defined to allocate tracheal and esophageal cell types is unknown. Here, we show that the EPH/EPHRIN signaling gene Efnb2 regulates tracheoesophageal separation by controlling the dorsoventral allocation of tracheal-fated cells. Ventral loss of NKX2-1 results in disruption of separation and expansion of Efnb2 expression in the trachea independent of SOX2. Through chromatin immunoprecipitation and reporter assays, we find that NKX2-1 likely represses Efnb2 directly. Lineage tracing shows that loss of NKX2-1 results in misallocation of ventral foregut cells into the esophagus, while mosaicism for Nkx2-1 generates ectopic NKX2-1/EPHRIN-B2 boundaries that organize ectopic tracheal separation. Together, these data demonstrate that NKX2-1 coordinates tracheal specification with tissue separation through the regulation of EPHRIN-B2 and tracheoesophageal cell sorting. |
