Unexpected functional redundancy between Twist and Slug (Snail2) and their feedback regulation of NF-kappaB via Nodal and Cerberus

Dev Biol. 2009 Jul 15;331(2):340-9. doi: 10.1016/j.ydbio.2009.04.016. Epub 2009 Apr 21.


A NF-kappaB-Twist-Snail network controls axis and mesoderm formation in Drosophila. Using translation-blocking morpholinos and hormone-regulated proteins, we demonstrate the presence of an analogous network in the early Xenopus embryo. Loss of twist (twist1) function leads to a reduction of mesoderm and neural crest markers, an increase in apoptosis, and a decrease in snail1 (snail) and snail2 (slug) mRNA levels. Injection of snail2 mRNA rescues twist's loss of function phenotypes and visa versa. In the early embryo NF-kappaB/RelA regulates twist, snail2, and snail1 mRNA levels; similarly Nodal/Smad2 regulate twist, snail2, snail1, and relA RNA levels. Both Twist and Snail2 negatively regulate levels of cerberus RNA, which encodes a Nodal, bone morphogenic protein (BMP), and Wnt inhibitor. Cerberus's anti-Nodal activity inhibits NF-kappaB activity and decreases relA RNA levels. These results reveal both conserved and unexpected regulatory interactions at the core of a vertebrate's mesodermal specification network.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / metabolism
  • Bone Morphogenetic Proteins / metabolism
  • Embryo, Nonmammalian
  • Feedback, Physiological
  • Gene Expression Regulation, Developmental
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Mesoderm / embryology
  • Mesoderm / metabolism
  • NF-kappa B / metabolism*
  • Neural Crest / embryology
  • Neural Crest / metabolism
  • Nodal Protein / metabolism*
  • Twist-Related Protein 1 / metabolism*
  • Xenopus / embryology
  • Xenopus / metabolism*
  • Xenopus Proteins / metabolism*


  • Antigens, Differentiation
  • Bone Morphogenetic Proteins
  • Intercellular Signaling Peptides and Proteins
  • NF-kappa B
  • Nodal Protein
  • Twist-Related Protein 1
  • Xenopus Proteins
  • cer1 protein, Xenopus