Yes-associated protein 65 (YAP) expands neural progenitors and regulates Pax3 expression in the neural plate border zone.
Yes-associated protein 65 (YAP) expands neural progenitors and regulates Pax3 expression in the neural plate border zone.
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DOI：
10.1371/journal.pone.0020309
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Moody SA
中科院分区：
文献类型：
--
作者：
Gee ST;Milgram SL;Kramer KL;Conlon FL;Moody SA
Yes 相关蛋白 65 (YAP) 包含多个蛋白质-蛋白质相互作用结构域，具有转录共激活因子和支架蛋白的功能。缺乏 YAP 的小鼠胚胎无法存活超过胚胎第 8.5 天，并显示出卵黄囊血管生成、绒毛膜尿囊融合和前后 (A-P) 轴伸长缺陷的迹象。鉴于 YAP 敲除小鼠的缺陷可能部分归因于营养缺乏，我们试图利用体外发育的胚胎更好地表征 YAP 在早期发育过程中的作用。 YAP 吗啉代 (MO) 介导的青蛙和鱼类功能丧失导致原肠胚形成时外胚层不完全和轴形成受损，类似于小鼠表型。在青蛙中，胚层特异性基因得到表达，但表达时间延迟。 YAP MO 介导的青蛙部分敲低导致轴缩短。爪蟾中的 YAP 功能获得扩大了神经板 (sox2+) 和神经板边界区 (pax3+) 中的祖细胞群，同时抑制神经板边界区衍生组织（神经嵴、前基板外胚层、孵化腺）以及表皮和体节肌的后期标记物的表达。 YAP 通过与 TEAD1 (N-TEF) 结合，在 pax3 5' 调控区内高度保守、先前未描述的 TEAD 结合位点直接调节 pax3 表达。结构/功能分析表明，YAP 的 PDZ 结合基序有助于抑制表皮和体节肌肉分化，但神经板和神经板边界区祖细胞库的扩展需要完整、完整的 YAP 蛋白。这些结果提供了对功能丧失和功能获得实验中 YAP 介导的基因表达变化的全面分析。此外，这是第一份使用 YAP 结构功能分析来确定 YAP 的哪一部分参与特定基因表达变化的报告，也是第一份显示 YAP 在调节 pax3 神经嵴表达中作用的直接体内证据的报告。
Yes-associated protein 65 (YAP) contains multiple protein-protein interaction domains and functions as both a transcriptional co-activator and as a scaffolding protein. Mouse embryos lacking YAP did not survive past embryonic day 8.5 and showed signs of defective yolk sac vasculogenesis, chorioallantoic fusion, and anterior-posterior (A-P) axis elongation. Given that the YAP knockout mouse defects might be due in part to nutritional deficiencies, we sought to better characterize a role for YAP during early development using embryos that develop externally. YAP morpholino (MO)-mediated loss-of-function in both frog and fish resulted in incomplete epiboly at gastrulation and impaired axis formation, similar to the mouse phenotype. In frog, germ layer specific genes were expressed, but they were temporally delayed. YAP MO-mediated partial knockdown in frog allowed a shortened axis to form. YAP gain-of-function in Xenopus expanded the progenitor populations in the neural plate (sox2+) and neural plate border zone (pax3+), while inhibiting the expression of later markers of tissues derived from the neural plate border zone (neural crest, pre-placodal ectoderm, hatching gland), as well as epidermis and somitic muscle. YAP directly regulates pax3 expression via association with TEAD1 (N-TEF) at a highly conserved, previously undescribed, TEAD-binding site within the 5′ regulatory region of pax3. Structure/function analyses revealed that the PDZ-binding motif of YAP contributes to the inhibition of epidermal and somitic muscle differentiation, but a complete, intact YAP protein is required for expansion of the neural plate and neural plate border zone progenitor pools. These results provide a thorough analysis of YAP mediated gene expression changes in loss- and gain-of-function experiments. Furthermore, this is the first report to use YAP structure-function analyzes to determine which portion of YAP is involved in specific gene expression changes and the first to show direct in vivo evidence of YAP's role in regulating pax3 neural crest expression.
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影响因子：
64.8
作者：
Lu, XW;Borchers, AGM;Tessier-Lavigne, M
通讯作者：
Tessier-Lavigne, M
影响因子：
64.8
作者：
JARRIAULT, S;BROU, C;ISRAEL, A
通讯作者：
ISRAEL, A
影响因子：
8
作者：
Ferrigno, O;Lallemand, F;Mauviel, A
通讯作者：
Mauviel, A
影响因子：
56.9
作者：
COFFMAN, C;HARRIS, W;KINTNER, C
通讯作者：
KINTNER, C
影响因子：
64.5
作者：
COFFMAN, CR;SKOGLUND, P;KINTNER, CR
通讯作者：
KINTNER, CR