Both excitatory and inhibitory neurons transiently form clusters at the outermost region of the developing mammalian cerebral neocortex

• Published in: Journal of comparative neurology (1911) Vol. 527; no. 10; pp. 1577 - 1597
• Main Authors: Shin, Minkyung, Kitazawa, Ayako, Yoshinaga, Satoshi, Hayashi, Kanehiro, Hirata, Yukio, Dehay, Colette, Kubo, Ken‐ichiro, Nakajima, Kazunori
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-07-2019; Wiley Subscription Services, Inc; Wiley
• Subjects: Developmental stages; Embryos; excitatory neuron; in utero electroporation (IUE); inhibitory interneuron; Interneurons; Life Sciences; mammalian neocortical development; Neurobiology; neuronal migration; Neurons and Cognition; Occipital lobe; primate neocortical development; primitive cortical zone (PCZ); primitive neuronal clusters; RRID:AB_10712211, AB_141607, AB_141708, AB_141709, AB_162542, AB_162543, AB_2068506, AB_2298772, AB_2340375, AB_2491093, AB_2535853, AB_2536180, AB_2539796, AB_300798, AB_305426, AB_634520; γ-Aminobutyric acid; in utero electroporation (IUE); RRID:AB_10712211, AB_141607, AB_141708, AB_141709, AB_162542, AB_162543, AB_2068506, AB_2298772, AB_2340375, AB_2491093, AB_2535853, AB_2536180, AB_2539796, AB_300798, AB_305426, AB_634520; mammalian neocortical development; excitatory neuron; primitive cortical zone (PCZ); neuronal migration; primitive neuronal clusters; primate neocortical development; inhibitory interneuron
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.24634

During development of the mammalian cerebral neocortex, postmitotic excitatory neurons migrate toward the outermost region of the neocortex. We previously reported that this outermost region is composed of densely packed relatively immature neurons; we named this region, which is observed during the late stage of mouse neocortical development, the “primitive cortical zone (PCZ).” Here, we report that postmigratory immature neurons spend about 1–1.5 days in the PCZ. An electron microscopic analysis showed that the neurons in the PCZ tend to be in direct contact with each other, mostly in a radial direction, forming “primitive neuronal clusters” with a height of 3–7 cells and a width of 1–2 cells. A time‐course analysis of fluorescently labeled neurons revealed that the neurons took their positions within the primitive clusters in an inside‐out manner. The neurons initially participated in the superficial part of the clusters, gradually shifted their relative positions downward, and then left the clusters at the bottom of this structure. GABAergic inhibitory interneurons were also found within the primitive clusters in the developing mouse neocortex, suggesting that some clusters are composed of both excitatory neurons and inhibitory interneurons. Similar clusters were also observed in the outermost region of embryonic day (E) 78 cynomolgus monkey occipital cortex and 23 gestational week (GW) human neocortices. In the primate neocortices, including human, the presumptive primitive clusters seemed to expand in the radial direction more than that observed in mice, which might contribute to the functional integrity of the primate neocortex.
Using immunohistochemistry, confocal imaging, and electron microscopic analysis, the authors describe “primitive neuronal clusters” in the outermost surface region of the neocortical cortical plate. The primitive neuronal clusters include both excitatory and inhibitory neurons, and are observed not only in the mouse but also in the monkey and human neocortex.