Wentong Hong1 · Pifang Gong1 · Xinjie Pan1 · Zhonggan Ren1 · Yitong Liu1 · Guibo Qi1 · Jun‑Liszt Li2,3 · Wenzhi Sun3,4 · Woo‑Ping Ge3 · Chun‑Li Zhang5 · Shumin Duan6 · Song Qin1,71 Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
2 Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
3 Chinese Institute for Brain Research, Beijing 102206, China
4 School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China
5 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA
6 Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health of China, Zhejiang University School of Medicine, Hangzhou 310058, China
7 State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200032, China
Abstract
Astrocytes are the largest glial population in the mammalian brain. However, we have a minimal understanding of astrocyte development, especially fate specification in different regions of the brain. Through lineage tracing of the progenitors of the third ventricle (3V) wall via in-utero electroporation in the embryonic mouse brain, we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall. Unexpectedly, radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types: radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon. With genetic fate mapping analysis, we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon. Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon. With transcriptomic analysis of the region-specific 3V wall and lateral ventricle (LV) wall, we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon. Together, these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.
Keywords
Radial glia; Astrocyte specifcation; Lineage tracing; Diencephalon; Third ventricle
