初级造血前体细胞来源于原肠晚期中胚层，可以产生的大量血细胞为胚胎细胞存活和快速增殖提供氧气。Wnt/β-catenin信号是初级造血发育所必需的，然而其在初级造血发育过程中的调控机制目前所知甚少。我们发现PRP19/CDC5L复合体成员BCAS2可以促进Wnt/β-catenin信号传导。初步的研究结果表明，斑马鱼bcas2在初级造血组织有特异表达，在初级造血发育过程中有重要作用。敲除BCAS2的小鼠MEF细胞核中几乎检测不到Wnt激活引起的β-catenin在核内的积聚。进一步的研究揭示，BCAS2可能通过两种方式调控Wnt/β-catenin信号通路：抑制细胞核β-catenin降解及阻止β-catenin出核。本项目将深入研究BCAS2在初级造血发育中的功能和分子机制。鉴于核内β-catenin蛋白降解的重要性，我们相信本项目的实施会取得重要的的概念性突性突破和原创性成果。

Hematopoiesis occurs in two successive waves, primitive and definitive hematopoiesis during vertebrate embryonic development. Primitive hematopoietic progenitors, which function in the rapid production of large numbers of erythroid cells that support the growth and survival of the embryo, are the first cell type specified from the mesoderm late in gastrulation. Wnt/β-catenin signaling is highly activited and required for primitive hematopoiesis, but the regulation of this pathway remains to investigate. During the screen for Wnt/β-catenin signaling pathway modulators, we identified BCAS2 (Breast cancer amplified sequence 2), the core component of CDC5L/PRP19 complex, could promote Wnt signaling transduction. Preliminary data showed that Zebrafish bcas2 is specifically expressed in primitive hematopoietic tissues and is essencial for blood cell formation. The depletion of BCAS2 in mouse MEF cells led to total loss of Wnt activition induced-nuclear accumulation of β-catenin. Our study also indicates that BCAS2 may increase Wnt signalling through preventing the degradation and also the nuclear export of β-catenin in the nucleus. In this proposal, we plan using zebrafish and mouse embryo as model systems to explore the fuction and molecular mechanisms of BCAS2 during primitive hematopoiesis. Given the potential importance of β-catenin degradation in the nucleus, our study will make conceptual breakthrough in the regulation of Wnt/β-catenin signaling.