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Biol Open March 15, 2012; 1 (3): 286-94.
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sizzled function and secreted factor network dynamics.

Studies on the role of the E-box binding transcription factor Snail2 (Slug) in the induction of neural crest by mesoderm (Shi et al., 2011) revealed an unexpected increase in the level of sizzled RNA in the dorsolateral mesodermal zone (DMLZ) of morphant Xenopus embryos. sizzled encodes a secreted protein with both Wnt and BMP inhibitor activities. Morpholino-mediated down-regulation of sizzled expression in one cell of two cell embryos or the C2/C3 blastomeres of 32-cell embryos, which give rise to the DLMZ, revealed decreased expression of the mesodermal marker brachyury and subsequent defects in neural crest induction, pronephros formation, and muscle patterning. Loss of sizzled expression led to decreases in RNAs encoding the secreted Wnt inhibitor SFRP2 and the secreted BMP inhibitor Noggin; the sizzled morphant phenotype could be rescued by co-injection of RNAs encoding Noggin and either SFRP2 or Dickkopf (a mechanistically distinct Wnt inhibitor). Together, these observations reveal that sizzled, in addition to its established role in dorsal-ventral patterning, is also part of a dynamic BMP and Wnt signaling network involved in both mesodermal patterning and neural crest induction.

PubMed ID: 23213419
PMC ID: PMC3507283
Article link: Biol Open
Grant support: [+]

Species referenced: Xenopus
Genes referenced: a2m bmp4 chd7 dkk1 myc myod1 nog sfrp2 snai1 snai2 sox9 szl tbx2 tbxt twist1 wnt8a
Morpholinos: szl MO2

Article Images: [+] show captions
References [+] :
Akkers, A hierarchy of H3K4me3 and H3K27me3 acquisition in spatial gene regulation in Xenopus embryos. 2009, Pubmed, Xenbase