Control of Cerebral Cortical Proliferation

哺乳动物大脑的绝大多数神经元是在胚胎发育期间产生的。因此，对发育中的细胞分裂进行精确的调控是必要的，以便在成熟时大脑的每个部分都有正确数量的细胞。大脑皮层是大脑的最大部分，它的发育是高度有序的：先天遗传程序和环境影响的组合共同作用，控制皮层形成过程中的细胞分裂。本项目将重点研究一种分裂细胞间的通讯在控制皮质细胞分裂程度中的作用。特别地，它将评估通过Eph受体酪氨酸激酶和ephrin配体的信号传导在调节大脑皮质细胞分裂中的影响。该项目使用培养或动物模型中的细胞，遗传学和表观遗传学方法，以及功能的获得和丧失范式来研究Eph信号在发育中的小鼠大脑皮层中产生适当细胞成分的作用。这个奖项将有助于培养未来的科学思想家。在本科生物系，首席研究员教授、指导和培训大学生，包括理科生和非理科生，以及神经科学研究生。此外，PI还积极参与促进科学事业，并通过与社区的外展工作，增加传统上在科学领域代表性不足的群体的数量。本项目所描述的研究将进一步加深我们对细胞间通讯在皮质生成中的作用的理解，并将大量的学生引入科学研究。

The vast majority of the neurons of the mammalian brain are generated during embryonic development. Thus, precise regulation of developmental cell division is necessary so that the correct number of cells populates each part of the brain in maturity. The cerebral cortex is the largest part of the brain and its development is especially highly ordered: a combination of innate genetic programs and environmental influences act together to control cell division during the formation of the cortex. This project will focus on the role of one kind of communication between dividing cell in controlling the extent of cortical cell division. In particular, it will assess the influences of signaling via the Eph receptor tyrosine kinases and the ephrin ligands in modulating cerebral cortical cell division. The project uses cells in culture or animal models, genetic and epigenetic approaches, and gain- and loss- of function paradigms to investigate the role of Eph signaling in producing the proper cellular composition in the developing mouse cerebral cortex. This award will serve to train future scientific thinkers. Housed in an undergraduate Biology Department, the Principal Investigator teaches, mentors, and trains college students, both science and non-science students, as well as Neuroscience graduate students. In addition, the PI is actively engaged in promoting careers in science and increasing the numbers of traditionally underrepresented groups in science through outreach work with the community. The studies described in this project will further our understanding of the role of cell-cell communication in corticogenesis and will introduce a large number of students to scientific research.