scholarly journals Modern human changes in regulatory regions implicated in cortical development

2019 ◽  
Author(s):  
Juan Moriano ◽  
Cedric Boeckx
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Cortical Development ◽  
Chromatin Modification ◽  
Modern Human ◽  
Physical Interaction ◽  
Regulatory Regions ◽  
Cell Gene Expression ◽  
Species Specific ◽  
And Control

AbstractRecent paleogenomic studies have highlighted a very small set of proteins carrying modern human-specific missense changes in comparison to our closest extinct relatives. Despite being frequently alluded to as highly relevant, species-specific differences in regulatory regions remain understudied. Here, we integrate data from paleogenomics, chromatin modification and physical interaction, and single-cell gene expression of neural progenitor cells to report a set of genes whose enhancers and/or promoters harbor modern human single nucleotide changes that appeared after the split from the Neanderthal/Denisovan lineage. These regulatory regions exert their functions at early stages of cortical development and control a set of genes among which those related to chromatin regulation stand out. This functional category has not yet figured prominently in modern human evolution studies. Specifically, we find an enrichment for the SETD1A histone methyltransferase complex, known to regulate WNT-signaling for the generation and proliferation of intermediate progenitor cells.

scholarly journals KIF20A/MKLP2 regulates the division modes of neural progenitor cells during cortical development

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Anqi Geng ◽  
Runxiang Qiu ◽  
Kiyohito Murai ◽  
Jiancheng Liu ◽  
Xiwei Wu ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Cortical Development ◽  
Neural Progenitor

scholarly journals NCAM regulates temporal specification of neural progenitor cells via profilin2 during corticogenesis

2019 ◽  
Vol 219 (1) ◽  
Author(s):  
Rui Huang ◽  
De-Juan Yuan ◽  
Shao Li ◽  
Xue-Song Liang ◽  
Yue Gao ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cortical Neurons ◽  
Actin Polymerization ◽  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Cortical Development ◽  
Neural Progenitor ◽  
Neural Cell Adhesion ◽  
Fate Decision ◽  
Temporal Specification

The development of cerebral cortex requires spatially and temporally orchestrated proliferation, migration, and differentiation of neural progenitor cells (NPCs). The molecular mechanisms underlying cortical development are, however, not fully understood. The neural cell adhesion molecule (NCAM) has been suggested to play a role in corticogenesis. Here we show that NCAM is dynamically expressed in the developing cortex. NCAM expression in NPCs is highest in the neurogenic period and declines during the gliogenic period. In mice bearing an NPC-specific NCAM deletion, proliferation of NPCs is reduced, and production of cortical neurons is delayed, while formation of cortical glia is advanced. Mechanistically, NCAM enhances actin polymerization in NPCs by interacting with actin-associated protein profilin2. NCAM-dependent regulation of NPCs is blocked by mutations in the profilin2 binding site. Thus, NCAM plays an essential role in NPC proliferation and fate decision during cortical development by regulating profilin2-dependent actin polymerization.

scholarly journals SEPT7 Interacts with KIF20A and Regulates the Proliferative State of Neural Progenitor Cells During Cortical Development

2019 ◽  
Vol 30 (5) ◽  
pp. 3030-3043 ◽  
Author(s):  
Runxiang Qiu ◽  
Qiu Runxiang ◽  
Anqi Geng ◽  
Jiancheng Liu ◽  
C Wilson Xu ◽  
...  
Keyword(s):  
Cell Division ◽  
Progenitor Cells ◽  
Neuronal Differentiation ◽  
Cell Fate ◽  
Neural Progenitor Cells ◽  
Cortical Development ◽  
Neural Progenitor ◽  
Mammalian Brain ◽  
Additional Cell ◽  
A Cell

Abstract Balanced proliferation and differentiation of neural progenitor cells (NPCs) are critical for brain development, but how the process is regulated and what components of the cell division machinery is involved are not well understood. Here we report that SEPT7, a cell division regulator originally identified in Saccharomyces cerevisiae, interacts with KIF20A in the intercellular bridge of dividing NPCs and plays an essential role in maintaining the proliferative state of NPCs during cortical development. Knockdown of SEPT7 in NPCs results in displacement of KIF20A from the midbody and early neuronal differentiation. NPC-specific inducible knockout of Sept7 causes early cell cycle exit, precocious neuronal differentiation, and ventriculomegaly in the cortex, but surprisingly does not lead to noticeable cytokinesis defect. Our data uncover an interaction of SEPT7 and KIF20A during NPC divisions and demonstrate a crucial role of SEPT7 in cell fate determination. In addition, this study presents a functional approach for identifying additional cell fate regulators of the mammalian brain.

scholarly journals Post-transcriptional mechanisms distinguish human and chimp forebrain progenitor cells

2019 ◽  
Author(s):  
Daniela A Grassi ◽  
Per Ludvik Brattås ◽  
Jeovanis G Valdés ◽  
Melinda Rezeli ◽  
Marie E Jönsson ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Transcriptional Control ◽  
Neural Progenitor Cells ◽  
Specific Expression ◽  
Control Of Gene Expression ◽  
Transcriptional Regulatory ◽  
Transcriptional Regulatory Mechanisms ◽  
Species Specific ◽  
High Level ◽  
Rna Levels

AbstractThe forebrain has expanded in size and complexity during hominoid evolution. The contribution of post-transcriptional control of gene expression to this process is unclear. Using in-depth proteomics in combination with bulk and single-cell RNA sequencing, we analyzed protein and RNA levels of almost 5,000 genes in human and chimpanzee forebrain neural progenitor cells. We found that species differences in protein expression level was often independent of RNA levels, and more frequent than transcriptomic differences. Low-abundant proteins were more likely to show species-specific expression levels, while proteins expressed at a high level appeared to have evolved under stricter constraints. Our study implicates a previously unappreciated broad and important role for post-transcriptional regulatory mechanisms in the evolution of the human forebrain.

scholarly journals Species-Specific Differential AhR Expression Protects Human Neural Progenitor Cells against Developmental Neurotoxicity of PAHs

2010 ◽  
Vol 118 (11) ◽  
pp. 1571-1577 ◽  
Author(s):  
Kathrin Gassmann ◽  
Josef Abel ◽  
Hanno Bothe ◽  
Thomas Haarmann-Stemmann ◽  
Hans F. Merk ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Developmental Neurotoxicity ◽  
Human Neural Progenitor Cells ◽  
Species Specific

scholarly journals Roots of the Malformations of Cortical Development in the Cell Biology of Neural Progenitor Cells

2022 ◽  
Vol 15 ◽  
Author(s):  
Chiara Ossola ◽  
Nereo Kalebic
Keyword(s):  
Cerebral Cortex ◽  
Progenitor Cells ◽  
Neural Progenitor Cells ◽  
Cortical Development ◽  
Neural Progenitor ◽  
Autism Spectrum ◽  
Model Systems ◽  
Cortical Plate ◽  
Malformations Of Cortical Development ◽  
Brain Functions

The cerebral cortex is a structure that underlies various brain functions, including cognition and language. Mammalian cerebral cortex starts developing during the embryonic period with the neural progenitor cells generating neurons. Newborn neurons migrate along progenitors’ radial processes from the site of their origin in the germinal zones to the cortical plate, where they mature and integrate in the forming circuitry. Cell biological features of neural progenitors, such as the location and timing of their mitoses, together with their characteristic morphologies, can directly or indirectly regulate the abundance and the identity of their neuronal progeny. Alterations in the complex and delicate process of cerebral cortex development can lead to malformations of cortical development (MCDs). They include various structural abnormalities that affect the size, thickness and/or folding pattern of the developing cortex. Their clinical manifestations can entail a neurodevelopmental disorder, such as epilepsy, developmental delay, intellectual disability, or autism spectrum disorder. The recent advancements of molecular and neuroimaging techniques, along with the development of appropriate in vitro and in vivo model systems, have enabled the assessment of the genetic and environmental causes of MCDs. Here we broadly review the cell biological characteristics of neural progenitor cells and focus on those features whose perturbations have been linked to MCDs.

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