Precise assembly of neural circuits in the brain underlies proper cognitive and mental functions. Over the past decades, increasing evidence suggest that defects in synaptic assembly are responsible for a spectrum of neurodevelopmental disorders such as autism and schizophrenia. However, little is known about the mechanisms that govern synaptic specificity in the mammalian central nervous system. To elucidate mechanisms underlying circuit assembly in a step-wise manner, I started by categorizing cell types within a neural ensemble, gaining genetic access to them, mapping their inter-connectivity and then identifying critical mediators for specific connectivity among the cells. These tests also led to the final examinations of the molecular functions in the circuits. Using the mouse retina as a model, I focused on the On-Off direction-selective circuits, which compute directions of motion before passing the information to the brain. However, it was not clear which of ten bipolar subtypes feed parallel ON and OFF visual information to the On-Off direction-selective ganglion cells (ooDSGCs). By establishing genetic drivers to mark and manipulate bipolar interneuron subtypes and further categorizing the cell-recognition molecules within the subtypes, I established a comprehensive circuit wiring diagram from bipolar interneurons to the ooDSGCs and demonstrated that two members of the classic cadherin family of molecules, Cdh8/Cdh9 play both instructive and permissive roles in Off/On bipolar cells respectively during the retinal circuit assembly. Furthermore, visually-evoked responses from the circuit, i.e. Off/On responses, were greatly compromised in the cdh8/cdh9 mutants. More generally, the results supported the hypothesis that the cadherin “adhesive code” regulates neural circuit assembly (Duan, et al, 2014, Cell; Duan et al, 2018, Neuron).
Similarly, using genetic access to the cell subtypes and identifying enriched genes within the cell types, I am also interested in probing other physiological questions in the CNS, such as axon regeneration following injury. By gaining genetic access to the retinal ganglion cell (RGC) subtypes and identifying enriched genes within particular subtypes, I investigated how different RGC subtypes regenerate their axons in response to injury. My work revealed dramatic subtype-specific differences among RGCs in terms of their ability to survive and regenerate. Furthermore, using transcriptomic approach, I identified osteopontin as a promising agent to facilitate axon regeneration (Duan, et al, Neuron, 2015).
Xin Duan was born in Shandong, China, matriculated at Tsinghua University in Beijing and graduated with Highest Honor. He then moved to the United States and attended the Johns Hopkins University School of Medicine for graduate studies in Neuroscience. Xin Duan was awarded the Young Investigator Award at Hopkins upon graduation and carried out postdoctoral training at the Laboratory of Dr. Joshua Sanes at Harvard University, where the research focused on retinal circuit wiring during development and rewiring subject to diseases and injuries. Xin Duan recently joined the Departments of Ophthalmology and Physiology at UCSF and is launching an independent research program on retina circuit study. He has a bold vision on developing and utilizing cutting-edge neuro-technology to wire retinal circuits and restore visual functions.
Sponsored by the NYU-ECNU Institute of Brain and Cognitive Science at NYU Shanghai