Topographical organization of mammillary neurogenesis and efferent projections in the mouse brain

• Published in: Cell reports (Cambridge) Vol. 34; no. 6; p. 108712
• Main Authors: Hou, Yongjie, Zhang, Qi, Liu, Hongzhi, Wu, Jinyun, Shi, Yun, Qi, Yanqing, Shao, Mengmeng, Yang, Zhengang, Lu, Jiangteng, Wu, Zhuhao, Gong, Ling, He, Miao
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.02.2021; Elsevier
• Subjects: Animals; Cell Differentiation; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fezf2; inducible genetic fate mapping; intersectional targeting; Mammillary Bodies - embryology; mammillary body; Mice; Mice, Knockout; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurogenesis; Neurons - metabolism; projection mapping; topographic principles; inducible genetic fate mapping; mammillary body; Fezf2; topographic principles; projection mapping; intersectional targeting
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2021.108712

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. [Display omitted] •Fezf2 is expressed in multipotent mammillary progenitors but not post-mitotically•Fezf2+ progenitors produce mammillary neurons in an outside-in fashion•Mammillary efferents from different temporal cohorts are topographically organized•Fezf2 is dispensable for mammillary neuron specification and projection Hou et al. identify progenitor-specific expression of Fezf2 in the embryonic mammillary region. They label different temporal cohorts of neurons by an intersectional method and uncover their rostral-dorsal-lateral to caudal-ventral-medial distribution and topographical organizations of their axonal projections. Fezf2 ablation reveals that it is dispensable for mammillary neuron specification and projection.