3D reconstruction of the cerebellar germinal layer reveals tunneling connections between developing granule cells

Diégo Cordero Cervantes (1, 2) , Harshavardhan Khare (1) , Alyssa Michelle Wilson (3) , Nathaly Dongo Mendoza (1, 4) , Orfane Coulon-Mahdi (1) , Jeff William Lichtman (5) , Chiara Zurzolo (1)

1 Trafic membranaire et Pathogénèse - Membrane Traffic and Pathogenesis
2 Université Paris-Saclay
3 MSSM - Icahn School of Medicine at Mount Sinai [New York]
4 UTEC - Universidad de Ingeniería y Tecnología [Lima, Peru]
5 Harvard University [Cambridge]

The difficulty of retrieving high-resolution, in vivo evidence of the proliferative and migratory processes occurring in neural germinal zones has limited our understanding of neurodevelopmental mechanisms. Here, we used a connectomic approach using a high-resolution, serial-sectioning scanning electron microscopy volume to investigate the laminar cytoarchitecture of the transient external granular layer (EGL) of the developing cerebellum, where granule cells coordinate a series of mitotic and migratory events. By integrating image segmentation, three-dimensional reconstruction, and deep-learning approaches, we found and characterized anatomically complex intercellular connections bridging pairs of cerebellar granule cells throughout the EGL. Connected cells were either mitotic, migratory, or transitioning between these two cell stages, displaying a chronological continuum of proliferative and migratory events never previously observed in vivo at this resolution. This unprecedented ultrastructural characterization poses intriguing hypotheses about intercellular connectivity between developing progenitors and its possible role in the development of the central nervous system.

Domains: Cellular Biology

Diégo Cordero Cervantes, Harshavardhan Khare, Alyssa Michelle Wilson, Nathaly Dongo Mendoza, Orfane Coulon-Mahdi, et al.. 3D reconstruction of the cerebellar germinal layer reveals tunneling connections between developing granule cells. Science Advances , 2023, 9 (14), pp.eadf347. ⟨10.1126/sciadv.adf3471⟩. ⟨pasteur-04065869v2⟩