Showing papers on "Radial glial cell published in 2019"

A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture

Abstract: Recognizable by its deep outer folds in humans, the cerebral cortex is a region of the mammalian brain which handles complex processes such as conscious perception or decision-making. It is organized in several layers that contain different types of ‘excitatory’ neurons which can activate other cells. The various areas of the cortex have different characteristics as they contain various proportions of each kind of neurons. Stem cells are cells capable to divide and create various types of specialized cells. The excitatory neurons in the cortex are created during development by stem cells known as radial glial cells. These cells divide several times, giving rise to different types of neurons in sucessive divisions, presumably thanks to internal molecular clocks. In the cortex, it is generally assumed that an individual radial glial cell produces all the different types of excitatory neurons. However, studies have suggested that certain cells could be specialized in creating specific types of neurons. To explore this question, Llorca et al. used three complementary approaches to follow individual radial glial cells and track the neurons they created in mouse embryos. This helped to understand how groups of stem cells work together to build the cortex. The experiments revealed that radial glial cells differ more than anticipated in the number and the types of neurons they generate, and rarely produce all types of excitatory neurons. In other words, the output of individual radial glial cells is not always the same. The results by Llorca et al. suggest that as radial glial cells divide, they undergo a series of probabilistic decisions – that is, in each division the cells have a certain probability to generate a specific type of neuron. Consequently, the resulting lineages are rarely identical or contain all types of excitatory neurons, but collectively they generate the full diversity of excitatory neurons in the cortex. Ultimately, new insights into how excitatory neurons form and connect in the brain may be used to help understand psychiatric conditions where circuits in the cortex might be impaired, such as in autism spectrum disorders.

Genes and Mechanisms Involved in the Generation and Amplification of Basal Radial Glial Cells.

Abstract: The development of the cerebral cortex relies on different types of progenitor cell. Among them, the recently described basal radial glial cell (bRG) is suggested to be of critical importance for the development of the brain in gyrencephalic species. These cells are highly numerous in primate and ferret brains, compared to lissencephalic species such as the mouse in which they are few in number. Their somata are located in basal subventricular zones in gyrencephalic brains and they generally possess a basal process extending to the pial surface. They sometimes also have an apical process directed toward the ventricular surface, similar to apical radial glial cells (aRGs) from which they are derived, and whose somata are found more apically in the ventricular zone. bRGs share similarities with aRGs in terms of gene expression (SOX2, PAX6, and NESTIN), whilst also expressing a range of more specific genes (such as HOPX). In primate brains, bRGs can divide multiple times, self-renewing and/or generating intermediate progenitors and neurons. They display a highly specific cytokinesis behavior termed mitotic somal translocation. We focus here on recently identified molecular mechanisms associated with the generation and amplification of bRGs, including bRG-like cells in the rodent. These include signaling pathways such as the FGF-MAPK cascade, SHH, PTEN/AKT, PDGF pathways, and proteins such as INSM, GPSM2, ASPM, TRNP1, ARHGAP11B, PAX6, and HIF1α. A number of these proteins were identified through transcriptome comparisons in human aRGs vs. bRGs, and validated by modifying their activities or expression levels in the mouse. This latter experiment often revealed enhanced bRG-like cell production, even in some cases generating folds (gyri) on the surface of the mouse cortex. We compare the features of the identified cells and methods used to characterize them in each model. These important data converge to indicate pathways essential for the production and expansion of bRGs, which may help us understand cortical development in health and disease.

ANO1/TMEM16A regulates process maturation in radial glial cells in the developing brain

Abstract: Neural stem cells (NSCs) are primary progenitor cells in the early developmental stage in the brain that initiate a diverse lineage of differentiated neurons and glia. Radial glial cells (RGCs), a type of neural stem cell in the ventricular zone, are essential for nurturing and delivering new immature neurons to the appropriate cortical target layers. Here we report that Anoctamin 1 (ANO1)/TMEM16A, a Ca2+-activated chloride channel, mediates the Ca2+-dependent process extension of RGCs. ANO1 is highly expressed and functionally active in RGCs of the mouse embryonic ventricular zone. Knockdown of ANO1 suppresses RGC process extension and protrusions, whereas ANO1 overexpression stimulates process extension. Among various trophic factors, brain-derived neurotrophic factor (BDNF) activates ANO1, which is required for BDNF-induced process extension in RGCs. More importantly, Ano1-deficient mice exhibited disrupted cortical layers and reduced cortical thickness. We thus conclude that the regulation of RGC process extension by ANO1 contributes to the normal formation of mouse embryonic brain.

A SMAD1/5-YAP signaling module drives radial glial cell expansion and growth of the developing cerebral cortex

Abstract: The growth and evolutionary expansion of the cerebral cortex are defined by the spatial-temporal production of neurons, which itself depends on the decision of radial glial cells (RGCs) to self-amplify or to switch to neurogenic divisions. The mechanisms regulating these RGC fate decisions are still incompletely understood. Here we describe a novel and evolutionarily conserved role of the canonical BMP transcription factors SMAD1/5 in controlling neurogenesis and growth during corticogenesis. Reducing the expression of both SMAD1 and SMAD5 in neural progenitors at early mouse cortical development caused microcephaly and an increased production of early-born cortical neurons at the expense of late-born ones, which correlated with the premature differentiation and depletion of the pool of cortical progenitors. Gain- and loss-of-function experiments performed during early cortical neurogenesis in the chick revealed that SMAD1/5 activity supports self-amplifying RGC divisions and restrain the neurogenic ones. Furthermore, we demonstrate that SMAD1/5 stimulate RGC self-amplification through the positive post-transcriptional regulation of the Hippo signaling effector YAP. We anticipate this SMAD1/5-YAP signaling module to be fundamental in controlling growth and evolution of the amniote cerebral cortex.