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Molecular Mechanisms of Asymmetric Cell Division in Neural Development and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 13071

Special Issue Editor


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Guest Editor
Developmental Neurobiology Department, Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas/Universidad Miguel Hernández, 03550 Sant Joan d’Alacant, Alicante, Spain
Interests: asymmetric cell division; neural stem cells; cell polarity; tumorigenesis; tumor suppressor genes

Special Issue Information

Dear Colleagues,

Asymmetric stem cell division (ASCD) is a fundamental and universal process to generate cell diversity during development and to modulate tissue homeostasis in the adult life. Besides, over the past decades, a connection between failures in the process of ASCD and tumorigenesis has become one of the most exciting findings in the field. Hence, understanding in depth the molecular mechanisms underlying the process of ASCD is of great relevance. Over the past few decades, we have also witnessed very significant advances on this topic, uncovering novel players and their mode of action to regulate ASCD. In this Special Issue, we aim to highlight this progress, provide novel and recent contributions, as well as to underscore the current challenges and future trends in the field.

I encourage the submission of both original research articles and topical reviews on all related aspects of ASCD.

Dr. Ana Carmena
Guest Editor

Manuscript Submission Information

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Keywords

  • asymmetric cell division
  • neural stem cells
  • cell polarity
  • spindle orientation
  • cell cycle
  • centrosomes
  • self-renewal/differentiation
  • tumorigenesis
  • brain tumors
  • brain disorders

Published Papers (4 papers)

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Research

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19 pages, 6017 KiB  
Article
Pilot RNAi Screen in Drosophila Neural Stem Cell Lineages to Identify Novel Tumor Suppressor Genes Involved in Asymmetric Cell Division
by Sandra Manzanero-Ortiz, Ana de Torres-Jurado, Rubí Hernández-Rojas and Ana Carmena
Int. J. Mol. Sci. 2021, 22(21), 11332; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111332 - 20 Oct 2021
Viewed by 1899
Abstract
A connection between compromised asymmetric cell division (ACD) and tumorigenesis was proven some years ago using Drosophila larval brain neural stem cells, called neuroblasts (NBs), as a model system. Since then, we have learned that compromised ACD does not always promote tumorigenesis, as [...] Read more.
A connection between compromised asymmetric cell division (ACD) and tumorigenesis was proven some years ago using Drosophila larval brain neural stem cells, called neuroblasts (NBs), as a model system. Since then, we have learned that compromised ACD does not always promote tumorigenesis, as ACD is an extremely well-regulated process in which redundancy substantially overcomes potential ACD failures. Considering this, we have performed a pilot RNAi screen in Drosophila larval brain NB lineages using RasV12 scribble (scrib) mutant clones as a sensitized genetic background, in which ACD is affected but does not cause tumoral growth. First, as a proof of concept, we have tested known ACD regulators in this sensitized background, such as lethal (2) giant larvae and warts. Although the downregulation of these ACD modulators in NB clones does not induce tumorigenesis, their downregulation along with RasV12 scrib does cause tumor-like overgrowth. Based on these results, we have randomly screened 79 RNAi lines detecting 15 potential novel ACD regulators/tumor suppressor genes. We conclude that RasV12 scrib is a good sensitized genetic background in which to identify tumor suppressor genes involved in NB ACD, whose function could otherwise be masked by the high redundancy of the ACD process. Full article
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Review

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14 pages, 1625 KiB  
Review
Regulation of Neural Stem Cell Competency and Commitment during Indirect Neurogenesis
by Arjun Rajan, Cyrina M. Ostgaard and Cheng-Yu Lee
Int. J. Mol. Sci. 2021, 22(23), 12871; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222312871 - 28 Nov 2021
Cited by 2 | Viewed by 2893
Abstract
Indirect neurogenesis, during which neural stem cells generate neurons through intermediate progenitors, drives the evolution of lissencephalic brains to gyrencephalic brains. The mechanisms that specify intermediate progenitor identity and that regulate stem cell competency to generate intermediate progenitors remain poorly understood despite their [...] Read more.
Indirect neurogenesis, during which neural stem cells generate neurons through intermediate progenitors, drives the evolution of lissencephalic brains to gyrencephalic brains. The mechanisms that specify intermediate progenitor identity and that regulate stem cell competency to generate intermediate progenitors remain poorly understood despite their roles in indirect neurogenesis. Well-characterized lineage hierarchy and available powerful genetic tools for manipulating gene functions make fruit fly neural stem cell (neuroblast) lineages an excellent in vivo paradigm for investigating the mechanisms that regulate neurogenesis. Type II neuroblasts in fly larval brains repeatedly undergo asymmetric divisions to generate intermediate neural progenitors (INPs) that undergo limited proliferation to increase the number of neurons generated per stem cell division. Here, we review key regulatory genes and the mechanisms by which they promote the specification and generation of INPs, safeguarding the indirect generation of neurons during fly larval brain neurogenesis. Homologs of these regulators of INPs have been shown to play important roles in regulating brain development in vertebrates. Insight into the precise regulation of intermediate progenitors will likely improve our understanding of the control of indirect neurogenesis during brain development and brain evolution. Full article
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13 pages, 501 KiB  
Review
Transcriptional Control of Apical-Basal Polarity Regulators
by Katja Rust and Andreas Wodarz
Int. J. Mol. Sci. 2021, 22(22), 12340; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222212340 - 15 Nov 2021
Cited by 4 | Viewed by 4372
Abstract
Cell polarity is essential for many functions of cells and tissues including the initial establishment and subsequent maintenance of epithelial tissues, asymmetric cell division, and morphogenetic movements. Cell polarity along the apical-basal axis is controlled by three protein complexes that interact with and [...] Read more.
Cell polarity is essential for many functions of cells and tissues including the initial establishment and subsequent maintenance of epithelial tissues, asymmetric cell division, and morphogenetic movements. Cell polarity along the apical-basal axis is controlled by three protein complexes that interact with and co-regulate each other: The Par-, Crumbs-, and Scrib-complexes. The localization and activity of the components of these complexes is predominantly controlled by protein-protein interactions and protein phosphorylation status. Increasing evidence accumulates that, besides the regulation at the protein level, the precise expression control of polarity determinants contributes substantially to cell polarity regulation. Here we review how gene expression regulation influences processes that depend on the induction, maintenance, or abolishment of cell polarity with a special focus on epithelial to mesenchymal transition and asymmetric stem cell division. We conclude that gene expression control is an important and often neglected mechanism in the control of cell polarity. Full article
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13 pages, 1268 KiB  
Review
Phase Separation and Mechanical Forces in Regulating Asymmetric Cell Division of Neural Stem Cells
by Yiqing Zhang, Heyang Wei and Wenyu Wen
Int. J. Mol. Sci. 2021, 22(19), 10267; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910267 - 24 Sep 2021
Cited by 6 | Viewed by 3132
Abstract
Asymmetric cell division (ACD) of neural stem cells and progenitors not only renews the stem cell population but also ensures the normal development of the nervous system, producing various types of neurons with different shapes and functions in the brain. One major mechanism [...] Read more.
Asymmetric cell division (ACD) of neural stem cells and progenitors not only renews the stem cell population but also ensures the normal development of the nervous system, producing various types of neurons with different shapes and functions in the brain. One major mechanism to achieve ACD is the asymmetric localization and uneven segregation of intracellular proteins and organelles into sibling cells. Recent studies have demonstrated that liquid-liquid phase separation (LLPS) provides a potential mechanism for the formation of membrane-less biomolecular condensates that are asymmetrically distributed on limited membrane regions. Moreover, mechanical forces have emerged as pivotal regulators of asymmetric neural stem cell division by generating sibling cell size asymmetry. In this review, we will summarize recent discoveries of ACD mechanisms driven by LLPS and mechanical forces. Full article
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