TGF-beta regulation of cell proliferation and differentiation in C. elegans

描述(由申请人提供)：细胞增殖和细胞命运规范之间的协调是发育的基础，这两个过程在癌症中都被错误地调控。虽然已知许多调节这些过程的分子途径，但它们在整个生物体背景下的相互作用却知之甚少。研究人员的长期目标是了解控制线虫生殖系增殖和细胞命运的发育和分子基础，作为这种相互作用的通用模型。包括哺乳动物在内的大多数动物的生殖细胞在发育过程中都会广泛增殖。这种增殖是产生足够的成体配子所必需的。最近，她发现了转化生长因子-β信号通路在促进线虫幼虫生殖系增殖中的作用。初步数据表明，这一作用不同于先前描述的同一条转化生长因子-β途径在Dauer决策过程中的作用，并且该途径的作用是非自主的。这位研究人员建议对缺陷背后的细胞机制进行表征。此外，她的数据揭示了在这一背景下高度保守的转化生长因子β和Notch信号通路之间的遗传相互作用。SE建议测试一个关于它们分子相互作用的特定假设：转化生长因子信号影响Notch配体的表达。如果数据反驳了她的假设，研究人员将采取更公正的方法，开始确定转化生长因子-β信号对生殖系增殖的影响的细胞和分子基础。这些研究可能会对细胞增殖控制的一般方面提供广泛适用的结果和见解，进一步加深对发育的基本理解，并可能产生对癌症的影响。 项目简介：转化生长因子β和Notch细胞信号通路在动物中高度保守，在发育过程中控制着许多重要的细胞过程，包括细胞增殖和细胞命运指定。这些过程和信号通路与许多疾病有关，尤其是癌症。这位研究人员最近发现了转化生长因子β在线虫生殖细胞增殖中的一个新角色。她建议使用这个简单的模式生物来研究转化生长因子-β信号和Notch通路之间的相互作用，因为它们影响生殖细胞的增殖和分化。

DESCRIPTION (Provided by Applicant): The coordination between cell proliferation and cell fate specification is fundamental to development and both processes are misregulated in cancer. While many molecular pathways are known that regulate these processes, their interactions in the whole-organism context are poorly understood. The investigator's long-term goal is to understand the developmental and molecular basis for the control of germline proliferation and cell fate specification in C. elegans as a general model for this interaction. The germ cells of most animals, including mammals, proliferate extensively during development. This proliferation is required to produce adequate adult gamete production. Recently, she discovered a role for the TGF-¿ signaling pathway in promoting C. elegans larval germline proliferation. Preliminary data suggest that this role is distinct from the previously characterized role for the same TGF-¿ pathway during the dauer decision, and that the pathway acts germline non-autonomously. The investigator proposes to characterize the cellular mechanisms underlying the defect. In addition, her data reveal a genetic interaction between the highly-conserved TGF-¿ and Notch signaling pathways in this context. Se proposes to test a specific hypothesis regarding their molecular interaction: that TGF-¿ signaling influences Notch ligand expression. Should the data refute her hypothesis, the investigator will take more unbiased approaches to begin to determine the cellular and molecular basis for the effect of TGF-¿ signaling on germline proliferation. These studies will likely provide broadly applicable results and insights into general aspects of cell proliferation control, furthering a basic understanding of development and possibly yielding implications for cancer. PROJECT NARRATIVE: The TGF-¿ and Notch cell signaling pathways are highly conserved in animals and govern many important cellular processes during development, including cell proliferation and cell fate specification. These processes and signaling pathways are implicated in many diseases, especially cancer. The investigator recently discovered a new role for TGF-¿ in germ cell proliferation in C. elegans. She proposes to use this simple model organism to investigate the interaction between TGF-¿ signaling and the Notch pathway as they impinge on germ cell proliferation and differentiation.