scholarly journals CAMSAPs organize an acentrosomal microtubule network from basal varicosities in radial glial cells

2021 ◽  
Vol 220 (8) ◽  
Author(s):  
Laure Coquand ◽  
Guiliana Soraya Victoria ◽  
Alice Tata ◽  
Jacopo Amerigo Carpentieri ◽  
Jean-Baptiste Brault ◽  
...  

Neurons of the neocortex are generated by stem cells called radial glial cells. These polarized cells extend a short apical process toward the ventricular surface and a long basal fiber that acts as a scaffold for neuronal migration. How the microtubule cytoskeleton is organized in these cells to support long-range transport is unknown. Using subcellular live imaging within brain tissue, we show that microtubules in the apical process uniformly emanate for the pericentrosomal region, while microtubules in the basal fiber display a mixed polarity, reminiscent of the mammalian dendrite. We identify acentrosomal microtubule organizing centers localized in varicosities of the basal fiber. CAMSAP family members accumulate in these varicosities, where they control microtubule growth. Double knockdown of CAMSAP1 and 2 leads to a destabilization of the entire basal process. Finally, using live imaging of human fetal cortex, we reveal that this organization is conserved in basal radial glial cells, a related progenitor cell population associated with human brain size expansion.

Author(s):  
L. Coquand ◽  
G.S. Victoria ◽  
A. Tata ◽  
J.B. Brault ◽  
F. Guimiot ◽  
...  

AbstractNeurons of the neocortex are generated by neural progenitors called radial glial cells. These polarized cells extend a short apical process towards the ventricular surface and a long basal fiber that acts as a scaffold for neuronal migration. How the microtubule cytoskeleton is organized in these cells to support long-range transport in unknown. Using subcellular live imaging within brain tissue, we show that microtubules in the apical process uniformly emanate for the pericentrosomal region, while microtubules in the basal fiber display a mixed polarity, reminiscent of the mammalian dendrite. We identify acentrosomal microtubule organizing centers localized in swellings of the basal fiber. We characterize their distribution and demonstrate that they accumulate the minus end stabilizing factor CAMSAP3 and TGN-related membranes, from which the majority of microtubules grow. Finally, using live imaging of human fetal cortex, we show that this organization is conserved in basal radial glial (bRG) cells, a highly abundant progenitor cell population associated with human brain size expansion.


2019 ◽  
Author(s):  
Muhammad Farooq ◽  
Louise Lindbæk ◽  
Nicolai Krogh ◽  
Canan Doganli ◽  
Cecilie Keller ◽  
...  

Introductory paragraphPrimary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability1. The exact pathophysiological mechanism underlying MCPH remains to be elucidated, but dysfunction of neuronal progenitors in the developing neocortex plays a major role1. Using homozygosity mapping and whole exome sequencing, we identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, which segregated with MCPH in a consanguineous family with 10 affected individuals. RRP7A is expressed in neural stem cells/radial glial cells of the developing human forebrain, and targeted mutation of Rrp7a leads to defects in both neurogenesis and proliferation in a mouse stem cell model. RRP7A localizes to centrosomes, cilia and nucleoli, and patient-derived fibroblasts display defects in processing of ribosomal RNA, resorption of primary cilia and cell cycle progression. Finally, analysis of zebrafish embryos with loss-of-function mutation in rrp7a confirmed that RRP7A depletion causes reduced brain size, impaired neurogenesis and cell proliferation as well as defective ribosomal RNA processing. These findings provide novel insight into human brain development and MCPH.


2008 ◽  
pp. 159-169
Author(s):  
Eckart Förster ◽  
Shanting Zhao ◽  
Michael Frotscher

2002 ◽  
Vol 69 (6) ◽  
pp. 708-713 ◽  
Author(s):  
Christopher T. Gregg ◽  
Andrew K. Chojnacki ◽  
Samuel Weiss

2018 ◽  
Vol 115 (40) ◽  
pp. 10142-10147 ◽  
Author(s):  
Brian G. Rash ◽  
Nicola Micali ◽  
Anita J. Huttner ◽  
Yury M. Morozov ◽  
Tamas L. Horvath ◽  
...  

The primary stem cells of the cerebral cortex are the radial glial cells (RGCs), and disturbances in their operation lead to myriad brain disorders in all mammals from mice to humans. Here, we found in mice that maternal gestational obesity and hyperglycemia can impair the maturation of RGC fibers and delay cortical neurogenesis. To investigate potential mechanisms, we used optogenetic live-imaging approaches in embryonic cortical slices. We found that Ca2+signaling regulates mitochondrial transport and is crucial for metabolic support in RGC fibers. Cyclic intracellular Ca2+discharge from localized RGC fiber segments detains passing mitochondria and ensures their proper distribution and enrichment at specific sites such as endfeet. Impairment of mitochondrial function caused an acute loss of Ca2+signaling, while hyperglycemia decreased Ca2+activity and impaired mitochondrial transport, leading to degradation of the RGC scaffold. Our findings uncover a physiological mechanism indicating pathways by which gestational metabolic disturbances can interfere with brain development.


Author(s):  
Magdalena Götz

This is a digitally enhanced text. Readers can also see the coverage of this topic area in the second edition of Neuroglia. The second edition of Neuroglia was first published digitally in Oxford Scholarship Online and the bibliographic details provided, if cited, will direct people to that version of the text. Readers can also see the coverage of this topic area in the ...


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