Topographical organization of mammillary neurogenesis and efferent projections in the mouse brain
Yongjie Hou,
Qi Zhang,
Hongzhi Liu,
Jinyun Wu,
Yun Shi,
Yanqing Qi,
Mengmeng Shao,
Zhengang Yang,
Jiangteng Lu,
Zhuhao Wu,
Ling Gong,
Miao He
Affiliations
Yongjie Hou
Institutes of Brain Science, Department of Neurology, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China
Qi Zhang
Institutes of Brain Science, Department of Neurology, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China
Hongzhi Liu
Institutes of Brain Science, Department of Neurology, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China
Jinyun Wu
Institutes of Brain Science, Department of Neurology, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China
Yun Shi
Institutes of Brain Science, Department of Neurology, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China
Yanqing Qi
Institutes of Brain Science, Department of Neurology, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China
Mengmeng Shao
Department of Anatomy and Physiology, Shanghai Jiaotong University School of Medicine, Shanghai, China
Zhengang Yang
Institutes of Brain Science, Department of Neurology, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China
Jiangteng Lu
Department of Anatomy and Physiology, Shanghai Jiaotong University School of Medicine, Shanghai, China
Zhuhao Wu
Department of Cell, Developmental and Regenerative Biology, Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Ling Gong
Institutes of Brain Science, Department of Neurology, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China; Corresponding author
Miao He
Institutes of Brain Science, Department of Neurology, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Zhongshan Hospital, Fudan University, Shanghai, China; Corresponding author
Summary: The mammillary body is a hypothalamic nucleus that has important functions in memory and spatial navigation, but its developmental principles remain not well understood. Here, we identify progenitor-specific Fezf2 expression in the developing mammillary body and develop an intersectional fate-mapping approach to demonstrate that Fezf2+ mammillary progenitors generate mammillary neurons in a rostral-dorsal-lateral to caudal-ventral-medial fashion. Axonal tracing from different temporal cohorts of labeled mammillary neurons reveal their topographical organization. Unsupervised hierarchical clustering based on intrinsic properties further identify two distinct neuronal clusters independent of birthdates in the medial nuclei. In addition, we generate Fezf2 knockout mice and observe the smaller mammillary body with largely normal anatomy and mildly affected cellular electrophysiology, in contrast to more severe deficits in neuronal differentiation and projection in many other brain regions. These results indicate that Fezf2 may function differently in the mammillary body. Our results provide important insights for mammillary development and connectivity.
