ZFIN ID: ZDB-PUB-200229-21
A gene regulatory network to control EMT programs in development and disease
Fazilaty, H., Rago, L., Kass Youssef, K., Ocaña, O.H., Garcia-Asencio, F., Arcas, A., Galceran, J., Nieto, M.A.
Date: 2019
Source: Nature communications   10: 5115 (Journal)
Registered Authors: Fazilaty, Hassan, Galceran, Juan, Nieto, Angela, Ocaña, Oscar H., Rago, Luciano
Keywords: none
MeSH Terms:
  • Animals
  • Cell Line
  • Chick Embryo
  • Epithelial-Mesenchymal Transition/genetics*
  • Gene Regulatory Networks*
  • Genetic Predisposition to Disease
  • Homeodomain Proteins
  • Humans
  • Mice, Inbred C57BL
  • MicroRNAs/metabolism
  • Prognosis
  • Promoter Regions, Genetic
  • Snail Family Transcription Factors/metabolism
  • Zebrafish/embryology
PubMed: 31712603 Full text @ Nat. Commun.
The Epithelial to Mesenchymal Transition (EMT) regulates cell plasticity during embryonic development and in disease. It is dynamically orchestrated by transcription factors (EMT-TFs), including Snail, Zeb, Twist and Prrx, all activated by TGF-β among other signals. Here we find that Snail1 and Prrx1, which respectively associate with gain or loss of stem-like properties and with bad or good prognosis in cancer patients, are expressed in complementary patterns during vertebrate development and in cancer. We show that this complementarity is established through a feedback loop in which Snail1 directly represses Prrx1, and Prrx1, through direct activation of the miR-15 family, attenuates the expression of Snail1. We also describe how this gene regulatory network can establish a hierarchical temporal expression of Snail1 and Prrx1 during EMT and validate its existence in vitro and in vivo, providing a mechanism to switch and select different EMT programs with important implications in development and disease.