XB-ART-39597Dev Biol July 15, 2009; 331 (2): 340-9.
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.
PubMed ID: 19389392
PMC ID: PMC2747320
Article link: Dev Biol
Genes referenced: a2m cer1 chrd.1 myod1 nfkb1 nodal nodal1 rela smad2 snai1 snai2 tbxt twist1 vegt
Morpholinos: snai2 MO1 twist1 MO1 twist1 MO2
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