Emerging roles for motor proteins in progenitor cell behavior and neuronal migration during brain development

Abstract Brain development comprises a fine-tuned ensemble of molecular processes that need to be orchestrated in a very coordinated way throughout time and space. A wide array of epigenetic mechanisms, ranging from DNA methylation and histone modifications to noncoding RNAs, have been identified for their major role in guiding developmental processes such as progenitor proliferation, neuronal migration, and differentiation through precise regulation of gene expression programs. The importance of epigenetic processes during development is reflected by the high prevalence of neurodevelopmental diseases which are caused by a lack or mutation of genes encoding for transcription factors and other epigenetic regulators. Most of these factors process central functions for proper brain development, and respective mutations lead to severe cognitive defects. A better understanding of epigenetic programs during development might open new routes toward better treatment options for related diseases.

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MARVELD1 depletion leads to dysfunction of motor and cognition via regulating glia-dependent neuronal migration during brain development

Cell Death and Disease ◽

10.1038/s41419-018-1027-6 ◽

2018 ◽

Vol 9 (10) ◽

Author(s):

Weizhe Liu ◽

Fang Han ◽

Shuai Qu ◽

Yuanfei Yao ◽

Jianxiang Zhao ◽

...

Keyword(s):

Brain Development ◽

Neuronal Migration

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Distinct progenitor behavior underlying neocortical gliogenesis related to tumorigenesis

10.1101/2020.10.13.338459 ◽

2020 ◽

Author(s):

Zhongfu Shen ◽

Yang Lin ◽

Jiajun Yang ◽

David J. Jörg ◽

Yuwei Peng ◽

...

Keyword(s):

Progenitor Cell ◽

Neurofibromatosis Type ◽

Primary Brain Tumor ◽

Precursor Cells ◽

Cell Behavior ◽

Neocortical Neurons ◽

Glial Progenitors ◽

Radial Glial ◽

Oligodendrocyte Precursor

SUMMARYRadial glial progenitors (RGPs) are responsible for producing the vast majority of neurons and glia in the neocortex. While RGP behavior and progressive generation of neocortical neurons have been delineated, the exact process of neocortical gliogenesis remains elusive. Here, we report the precise progenitor cell behavior and gliogenesis program at single-cell resolution in the mouse neocortex. RGPs transition from neurogenesis to gliogenesis progressively, producing astrocytes, oligodendrocytes, or both in well-defined propensities of 60%:15%:25%, respectively, via fate-restricted “intermediate” precursor cells. While the total number of precursor cells generated by individual RGPs appears stochastic, the output of individual precursor cells exhibit clear patterns in number and subtype, and form discrete local subclusters. Clonal loss of tumor suppressor Neurofibromatosis type 1 leads to excessive production of glia selectively, especially oligodendrocyte precursor cells. These results delineate the cellular program of neocortical gliogenesis quantitatively and suggest the cellular and lineage origin of primary brain tumor.

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Chemo-Mechanical Cues Modulate Nano-Scale Chromatin Organization in Healthy and Diseased Connective Tissue Cells

10.1101/2021.04.27.441596 ◽

2021 ◽

Author(s):

Su-Jin Heo ◽

Shreyasi Thakur ◽

Xingyu Chen ◽

Claudia Loebel ◽

Boao Xia ◽

...

Keyword(s):

Histone Methylation ◽

Genetic Information ◽

Progenitor Cell ◽

Fibrous Tissue ◽

Cell Behavior ◽

Environmental Cues ◽

Chromatin Dynamics ◽

Phenotypic Changes ◽

Nano Scale ◽

Tissue Cells

AbstractMicroscale changes in tissue environment are translated to changes in cell behavior and phenotype, yet the mechanisms behind how these phenotypic changes occur are poorly understood. Here, we describe and model chromatin, which stores genetic information within the cell nucleus, as a dynamic nanomaterial whose configuration is modulated by chemo-mechanical cues in the microenvironment. Our findings indicate that physiologic chemo-mechanical cues can directly regulate chromatin architecture in progenitor cell populations. Via direct experimental observation and modeling that incorporates phase transitions and histone methylation kinetics, we demonstrate that soft environmental cues drive chromatin relocalization to the nuclear boundary and compaction. Conversely, dynamic stiffening attenuates these changes. Interestingly, in diseased human fibrous tissue cells, this link between mechanical inputs and chromatin nano-scale remodeling is abrogated. These data indicate that chromatin dynamics and plasticity may be hallmarks of disease progression and targets for therapeutic intervention.

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