Unexpected functional redundancy between Twist and Slug (Snail2) and their feedback regulation of NF-kappaB via Nodal and Cerberus.
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.
Zhang
Chi
C
University of Colorado, Boulder, 80309-0347, USA.
Klymkowsky
Michael W
MW
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009432:Neural Crest / Q000196:embryology / Q000378:metabolism; D055457:Nodal Protein / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D014981:Xenopus / Q000196:embryology / Q000378:metabolism*; D029867:Xenopus Proteins / Q000378:metabolism*
D000943:Antigens, Differentiation; D019485:Bone Morphogenetic Proteins; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D055457:Nodal Protein; D051879:Twist-Related Protein 1; D029867:Xenopus Proteins; C100866:cer1 protein, Xenopus