Molecular, Cellular and Developmental Biology, University of Colorado , Boulder, CO 80309-0347 , USA.
Biol Open. 2012 Mar 15;1(3):286-94. doi: 10.1242/bio.2012019. Epub 2012 Feb 3.
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.
研究中胚层诱导神经嵴过程中 E 盒结合转录因子 Slug（Snail2）的作用（Shi 等人，2011）表明，在中胚层背外侧区（DMLZ）的形态发生胚胎中，sizzled RNA 的水平出人意料地增加。sizzled 编码一种具有 Wnt 和 BMP 抑制剂活性的分泌蛋白。在二细胞胚胎的一个细胞或 32 细胞胚胎的 C2/C3 卵裂球中，通过 morpholino 介导 sizzled 表达下调，导致中胚层标记物 brachyury 的表达减少，随后神经嵴诱导、前肾形成和肌肉模式化缺陷。sizzled 表达缺失导致编码分泌型 Wnt 抑制剂 SFRP2 和分泌型 BMP 抑制剂 Noggin 的 RNA 减少；Noggin 和 SFRP2 或 Dickkopf（一种机制上不同的 Wnt 抑制剂）的 RNA 共注射可挽救 sizzled 形态发生缺陷表型。总之，这些观察结果表明，sizzled 除了在背腹模式形成中的既定作用外，还是参与中胚层模式形成和神经嵴诱导的动态 BMP 和 Wnt 信号网络的一部分。
