A  Complex Code of Extrinsic Influences on Cortical Progenitor Cells of Higher Mammals

Abstract

Development of the cerebral cortex depends critically on the regulation of progenitor cell proliferation and fate. Cortical progenitor cells are remarkably diverse with regard to their morphology as well as laminar and areal position. Extrinsic factors, such as thalamic axons, have been proposed to play key roles in progenitor cell regulation, but the diversity, extent and timing of interactions between extrinsic elements and each class of cortical progenitor cell in higher mammals remain undefined. Here we use the ferret to demonstrate the existence of a complex set of extrinsic elements that may interact, alone or in combination, with subpopulations of progenitor cells, defining a code of extrinsic influences. This code and its complexity vary significantly between developmental stages, layer of residence and morphology of progenitor cells. By analyzing the spatial-temporal overlap of progenitor cell subtypes with neuronal and axonal populations, we show that multiple sets of migrating neurons and axon tracts overlap extensively with subdivisions of the Subventricular Zones, in an exquisite lamina-specific pattern. Our findings provide a framework for understanding the feedback influence of both intra- and extra-cortical elements onto progenitor cells to modulate their dynamics and fate decisions in gyrencephalic brains.

A Human Accelerated Region participates in early human forebrain patterning and expansion

“…In addition, gain-offunction experiments, either in transgenic HAR-14q12 mice or targeted humanized mouse ESC-derived 3D forebrain organoids resulted in the expansion of neuroepithelial and radial glia progenitors. Our results provide an additional mechanism that has potentially contributed to the shorter cell cycle and higher proliferative potential of RG progenitors, which is proposed to drive the evolutionary expansion of the mammalian telencephalon (Calegari et al, 2005;Pilz et al, 2013;Betizeau et al, 2013;Pilaz et al, 2009;Reillo et al, 2017).…”

Neocortical Expansion Due to Increased Proliferation of Basal Progenitors Is Linked to Changes in Their Morphology

“…bRG in hNcx exhibited a greater average number of radial processes than bRG in fNcx and mNcx. In addition to the radial processes, we detected a number of smaller protrusions of bRG, previously termed lamellate expansions (Rakic, 1972;Reillo et al, 2017), in hNcx and fNcx, but not mNcx (Figures 2C 00 ,S2O,and S2P).…”

“…BPs in ferret and primates show diverse morphologies (Betizeau et al, 2013;Reillo et al, 2017), some of which have also been observed in mNcx (Pilz et al, 2013;Wong et al, 2015). bRG were originally described as monopolar cells with a long basal process that often contacts the basal lamina (Fietz et al, 2010;Hansen et al, 2010;Reillo et al, 2011).…”

Multimodal Single-Cell Analysis Reveals Physiological Maturation in the Developing Human Neocortex

“…(legend continued on next page) and influence progenitor cell proliferation, neuronal migration, and differentiation in rodents (Le Magueresse and Monyer, 2013;LoTurco et al, 1995;Weissman et al, 2004). Progenitor cells, maturing excitatory neurons and interneurons, endothelial cells, and the cerebrospinal fluid (CSF) are all potential sources of neurotransmitters (Bonnin et al, 2011;Le Magueresse and Monyer, 2013;Lehtinen et al, 2011;Li et al, 2018;Manent et al, 2005;Reillo et al, 2017;Weissman et al, 2004). Additionally, axons from extracortical regions such as the diencephalon and brain stem innervate the cortex and affect cortical development (Bonetti and Surace, 2010;Chen and Kriegstein, 2015;Duque et al, 2016;Reillo et al, 2017).…”