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特化之间的协调是发育的基础，并且这两个过程在癌症中被错误调节。 虽然已知许多分子途径调节这些过程，但它们在整个生物体背景下的相互作用知之甚少。 研究者的长期目标是了解C. elegans作为这种相互作用的一般模型。 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广泛增殖。 这种增殖是产生足够的成年配子所必需的。 最近，她发现了TGF-β信号通路在促进C.线虫幼虫生殖系增殖。 初步的数据表明，这种作用是不同的，从以前的特点相同的TGF-β通路的作用，在dauer决定，和该途径的作用种系非自主。 研究者建议表征缺陷背后的细胞机制。 此外，她的数据揭示了高度保守的TGF-β和Notch信号通路之间的遗传相互作用。 Se提出测试关于它们的分子相互作用的特定假设：TGF-β信号传导影响Notch配体表达。 如果数据反驳了她的假设，研究者将采取更公正的方法来开始确定TGF-β信号传导对生殖系增殖影响的细胞和分子基础。 这些研究可能会提供广泛适用的结果和对细胞增殖控制的一般方面的见解，进一步了解发展的基本认识，并可能产生对癌症的影响。 项目叙述：TGF-β Notch和Notch细胞信号传导途径在动物中高度保守，并在发育期间控制许多重要的细胞过程，包括细胞增殖和细胞命运特化。 这些过程和信号通路与许多疾病，特别是癌症有关。 研究人员最近发现了TGF-β在C.优雅 她建议使用这种简单的模式生物来研究TGF-β信号传导和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.