dnase1l1在器官左右不对称模式建成中的作用及机制研究

器官左右不对称模式建成是胚胎早期发育的一重要事件，其具体调控机制不明。我们发现斑马鱼dnase1l1在DFCs中高表达，在环境压力而非正常发育环境下其功能敲降导致DFCs减少、KV/纤毛发育及器官左右不对称建成受损。由于小鼠Dnase1l3突变导致细胞凋亡受阻，而凋亡细胞对非凋亡细胞具有增殖诱导作用，因此我们推测在环境压力下，dnase1l1可能通过促进凋亡DFCs正常凋亡以诱导非凋亡DFCs增殖来维持DFCs数量稳态，调控器官左右不对称模式建成。本项目拟首先研究dnase1l1在器官左右不对称模式建成中的作用及其是否以促进凋亡DFCs的凋亡以诱导非凋亡DFCs增殖来调控器官左右不对称模式建成，然后阐明凋亡DFCs诱导非凋亡DFCs增殖的分子机制。本研究将有助于我们对胚胎在面对环境压力时其调控器官正常发育的分子调控机制的认识，也有望为器官左右不对称紊乱相关先天性疾病的防治提供理论依据。

Organ left-right asymmetry patterning is an important event in early embryo development, while its specific regulatory mechanism is largely unknown. we found that zebrafish dnase1l1 was highly expressed in DFCs, and under environmental stress while not normal developmental enviroment dnase1l1 loss of function led to the number of DFCs decrease, impaired KV/cilia development and subsquent organ left-right asymmetry patterning defect. Since Dnase1l3 mutation had been reported to cause apoptosis delaying, and apoptotic cells had also been reported to have the role inducing non-apoptotic cells proliferation, we speculated that, under environmental stress, dnase1l1 may maintain DFCs quantitative homeostasis by promoting apoptosis to induce non-apoptotic DFCs proliferation, then regulating organ left-right asymmetry patterning. Our project intends to, firstly investigate the role of dnase1l1 in the establishment of organ left-right asymmetry patterning and, investigate whether dnase1l1 regulates organ left-right asymmetry patterning by promoting apoptosis DFCs to induce non-apoptotic DFCs proliferation. Then we will elucidate how the apoptosis DFCs induce non-apoptotic DFCs proliferation. This study is expected to help us understand the molecular mechanism how embryos regulate the organ normal development under environmental stress, and also will provide theoretical guidance for the prevention and treatment of congenital diseases associated with organ left-right asymmetry defect.