大脑是我们人体内最为复杂的器官。作为我们神经系统的高级中枢，人类大脑由上千亿个神经元、大致相同数量的非神经元细胞和数万亿个神经连接组成，从组装到运行都异常复杂和精妙。这些神经细胞不但数量庞大、种类繁多，还需在合适的时间和地点产生，才可能建立正确的神经连接，进而支持我们诸如思维、认知、学习、语言等高级神经活动。大脑发育异常可能导致儿童脑瘤、小脑症、自闭症等诸多神经发育疾病。深入解析神经发育的分子调控机理是防治相关神经发育疾病的基础和关键。
课题组通过将全脑亚细胞结构长时程活体动态成像技术与果蝇遗传学、小鼠遗传学、液-液相分离、细胞生物学、生物化学及多组学等手段相结合，现阶段特别感兴趣的科学问题包括：
1.细胞命运记忆传承：脑发育过程中细胞如何在有丝分裂后及时“记住”或“遗忘”其细胞命运或身份？
2.神经发育时程解码：神经发育的时程信号如何被及时、精确读取并转换成细胞命运决策事件，确保神经元多样性的产生和维持？
3.专属基因表达程序：大脑作为人体最复杂的器官，其发育过程是否有其独特的基因表达程序？这个专属程序如何运行，其运行错误如何导致相关神经发育疾病的发生？
代表性论文
1. Shen Y., Liu K., Liu J., Shen J., Ye T., Zhao R., Zhang R. and Song Y.* (2024) TBP bookmarks and preserves neural stem cell fate memory by orchestrating local chromatin architecture. Molecular Cell, doi.org/10.1016/j.molcel.2024.11.019
2. Liu X.#, Shen J.#, Xie L., Wei Z., Wong C., Li Y., Zheng X., Li P. and Song Y.* (2020) Mitotic implantation of the transcription factor Prospero via phase separation drives terminal neuronal differentiation. Developmental Cell, 52(3), 277-293 [Featured article].
3. Li B.#, Wong C.#, Gao S.M., Zhang R., Sun R., Li Y. and Song Y.* (2018) The retromer complex safeguards against neural progenitor-derived tumorigenesis by regulating Notch receptor trafficking. Elife, 2018;7;e38181
4. Liu K., Shen D., Shen J., Gao S.M., Li B., Wong C., Feng W. and Song Y.* (2017) The super elongation complex drives neural stem cell fate commitment. Developmental Cell, 40(6), 537-551 [Cover article].
5. Xu K., Liu X., Wang Y., Wong C. and Song Y.* (2018) Temporospatial induction of homeodomain gene cut dictates natural lineage reprogramming. Elife, 2018;7:e33934
6. Liu K., Xu K. and Song Y.* (2019) Faster, Higher, Stronger: Timely and robust cell fate/identity commitment in stem cell lineages. Open Biology, 9: 180243. [Invited review]
7. Lee K.S.#, Wu Z.#, Song Y., Mitra S.S., Feroze A.H., Cheshier S.H., Lu B.* (2013) Roles of PINK1, mTORC2, and mitochondria in preserving brain tumor-forming stem cells in a noncanonical Notch signaling pathway. Genes & Development, 27(24):2642-7 [Cover article]
8. Song Y. and Lu B.* (2011) Regulation of cell growth by Notch signaling and its differential requirement in normal vs. tumor-forming stem cells in Drosophila. Genes & Development, 25(24):2644-2658.
