Marcks调节斑马鱼原肠胚形成中Bmp分泌和转运的机制研究

The patterning of embryonic dorsal-ventral axis is one of the most attractive issues for embryonic polarity and fate map formation. Bmp, as an important morphogen, is an inducer of ventral and lateral tissues. The study on how Bmp secrets and transports is an important aspect of dorsal-ventral patterning. Previously, our lab identified a differently expressed protein, Marcksb, in zebrafish gastrulation stages. Further study showed that knockdown of marcksb led to defective gastrulation and severe dorsalization. More importanlty, the ventralization induced by bmp2b overexpression could be partially rescued by knockingdown of marcksb. Intriguingly, Bmp proteins could not be detected outside of Bmp-source cells in marcksb-deficient embryos. Thus, we speculated that Marcksb regulates the secretion or transportation of Bmp. This study will focus on functional study of MARCKS family members in secretion and transport of Bmp as well as in gastrulation movements, mainly by means of living cell imaging and cell biology. It will help us to understand the mechanism for the formation of fine Bmp gradient, as well as new insight for dorsal-ventral patterning.

胚胎背腹轴的形成是胚胎极性决定和命运图谱形成的重要命题之一。Bmp作为一种重要的形态生成素，是腹侧组织和旁侧组织命运诱导因子，对其分泌和转运调控机理的研究是阐明背腹轴形成机制的重要基础。本学科组在前期研究中筛选到斑马鱼原肠胚形成时期的差异表达蛋白Marcksb；进一步研究发现敲降marcksb导致胚胎原肠运动缺陷和严重背部化，marcksb的部分敲降能够拯救bmp2b过表达所导致的严重腹部化表型。有趣的是，在marcksb缺陷胚胎中，Bmp蛋白不能在源细胞以外的胞内或胞外检测到，这提示Marcksb可能参与调控Bmp的分泌和转运。本课题拟通过活体细胞影像学和细胞生物学等方法，研究Bmp分泌和转运的方式（胞吐，胞吞或是特化的丝状伪足），并借助MARCKS家族基因突变模型，开展原肠运动和Bmp分泌和转运机理的研究。该研究将有助于我们认识胚胎背腹轴形成中Bmp分泌和转运的机制。