scholarly journals Antagonistic Effects of Grg6 and Groucho/TLE on the Transcription Repression Activity of Brain Factor 1/FoxG1 and Cortical Neuron Differentiation

2005 ◽  
Vol 25 (24) ◽  
pp. 10916-10929 ◽  
Author(s):  
Nathalie Marçal ◽  
Harshila Patel ◽  
Zhifeng Dong ◽  
Stephanie Belanger-Jasmin ◽  
Brad Hoffman ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Cortical Neuron ◽  
Neuronal Differentiation ◽  
Transcriptional Repression ◽  
Wd40 Repeat ◽  
Forkhead Transcription Factor ◽  
Proliferating Cells ◽  
Functional Link ◽  
Repeat Domain ◽  
Brain Factor

ABSTRACT Groucho (Gro)/TLE transcriptional corepressors are involved in a variety of developmental mechanisms, including neuronal differentiation. They contain a conserved C-terminal WD40 repeat domain that mediates interactions with several DNA-binding proteins. In particular, Gro/TLE1 interacts with forkhead transcription factor brain factor 1 (BF-1; also termed FoxG1). BF-1 is an essential regulator of neuronal differentiation during cerebral cortex development and represses transcription together with Gro/TLE1. Gro/TLE-related gene product 6 (Grg6) shares with Gro/TLEs a conserved WD40 repeat domain but is more distantly related at its N-terminal half. We demonstrate that Grg6 is expressed in cortical neural progenitor cells and interacts with BF-1. In contrast to Gro/TLE1, however, Grg6 does not promote, but rather suppresses, BF-1-mediated transcriptional repression. Consistent with these observations, Grg6 interferes with the binding of Gro/TLE1 to BF-1 and does not repress transcription when targeted to DNA. Moreover, coexpression of Grg6 and BF-1 in cortical progenitor cells leads to a decrease in the number of proliferating cells and increased neuronal differentiation. Conversely, Grg6 knockdown by RNA interference causes decreased neurogenesis. These results identify a new role for Grg6 in cortical neuron development and establish a functional link between Grg6 and BF-1.

scholarly journals Wild-Type and Mutant FUS Expression Reduce Proliferation and Neuronal Differentiation Properties of Neural Stem Progenitor Cells

2021 ◽  
Vol 22 (14) ◽  
pp. 7566
Author(s):  
Eleonora Stronati ◽  
Stefano Biagioni ◽  
Mario Fiore ◽  
Mauro Giorgi ◽  
Giancarlo Poiana ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Neuronal Differentiation ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Nervous System Development ◽  
Mutant Form ◽  
Wild Type ◽  
Fused In Sarcoma ◽  
Glial Lineage

Nervous system development involves proliferation and cell specification of progenitor cells into neurons and glial cells. Unveiling how this complex process is orchestrated under physiological conditions and deciphering the molecular and cellular changes leading to neurological diseases is mandatory. To date, great efforts have been aimed at identifying gene mutations associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Mutations in the RNA/DNA binding protein Fused in Sarcoma/Translocated in Liposarcoma (FUS/TLS) have been associated with motor neuron degeneration in rodents and humans. Furthermore, increased levels of the wild-type protein can promote neuronal cell death. Despite the well-established causal link between FUS mutations and ALS, its role in neural cells remains elusive. In order to shed new light on FUS functions we studied its role in the control of neural stem progenitor cell (NSPC) properties. Here, we report that human wild-type Fused in Sarcoma (WT FUS), exogenously expressed in mouse embryonic spinal cord-derived NSPCs, was localized in the nucleus, caused cell cycle arrest in G1 phase by affecting cell cycle regulator expression, and strongly reduced neuronal differentiation. Furthermore, the expression of the human mutant form of FUS (P525L-FUS), associated with early-onset ALS, drives the cells preferentially towards a glial lineage, strongly reducing the number of developing neurons. These results provide insight into the involvement of FUS in NSPC proliferation and differentiation into neurons and glia.

scholarly journals Distinct p63 and p73 Protein Interactions Predict Specific Functions in mRNA Splicing and Polyploidy Control in Epithelia

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 25
Author(s):  
Julian M. Rozenberg ◽  
Olga S. Rogovaya ◽  
Gerry Melino ◽  
Nickolai A. Barlev ◽  
Alexander Kagansky
Keyword(s):  
Protein Interactions ◽  
Transcriptional Repression ◽  
Genome Stability ◽  
Spindle Assembly Checkpoint ◽  
Genotoxic Stress ◽  
Protein Protein Interactions ◽  
Proliferating Cells ◽  
P53 Family ◽  
Differentiated Cells ◽  
Specific Localization

Epithelial organs are the first barrier against microorganisms and genotoxic stress, in which the p53 family members p63 and p73 have both overlapping and distinct functions. Intriguingly, p73 displays a very specific localization to basal epithelial cells in human tissues, while p63 is expressed in both basal and differentiated cells. Here, we analyse systematically the literature describing p63 and p73 protein–protein interactions to reveal distinct functions underlying the aforementioned distribution. We have found that p73 and p63 cooperate in the genome stability surveillance in proliferating cells; p73 specific interactors contribute to the transcriptional repression, anaphase promoting complex and spindle assembly checkpoint, whereas p63 specific interactors play roles in the regulation of mRNA processing and splicing in both proliferating and differentiated cells. Our analysis reveals the diversification of the RNA and DNA specific functions within the p53 family.

scholarly journals Large-scale generation of human iPSC-derived neural stem cells/early neural progenitor cells and their neuronal differentiation

Organogenesis ◽  
2014 ◽  
Vol 10 (4) ◽  
pp. 365-377 ◽  
Author(s):  
Leonardo D’Aiuto ◽  
Yun Zhi ◽  
Dhanjit Kumar Das ◽  
Madeleine R Wilcox ◽  
Jon W Johnson ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Progenitor Cells ◽  
Neuronal Differentiation ◽  
Large Scale ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Human Ipsc

Presenilin-1 regulates neuronal differentiation during neurogenesis

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2593-2606 ◽  
Author(s):  
M. Handler ◽  
X. Yang ◽  
J. Shen
Keyword(s):  
Cell Death ◽  
Progenitor Cells ◽  
Neuronal Differentiation ◽  
Cell Fate ◽  
Neural Progenitor Cells ◽  
Apoptotic Cell ◽  
Ventricular Zone ◽  
Neural Progenitor ◽  
Apoptotic Cell Death ◽  
Presenilin 1

Mutations in Presenilin-1 (PS1) are a major cause of familial Alzheimer's disease. Our previous studies showed that PS1 is required for murine neural development. Here we report that lack of PS1 leads to premature differentiation of neural progenitor cells, indicating a role for PS1 in a cell fate decision between postmitotic neurons and neural progenitor cells. Neural proliferation and apoptotic cell death during neurogenesis are unaltered in PS1(−/−) mice, suggesting that the reduction in the neural progenitor cells observed in the PS1(−/−) brain is due to premature differentiation of progenitor cells, rather than to increased apoptotic cell death or decreased cell proliferation. In addition, the premature neuronal differentiation in the PS1(−/−) brain is associated with aberrant neuronal migration and disorganization of the laminar architecture of the developing cerebral hemisphere. In the ventricular zone of PS1(−/−) mice, expression of the Notch1 downstream effector gene Hes5 is reduced and expression of the Notch1 ligand Dll1 is elevated, whereas expression of Notch1 is unchanged. The level of Dll1 transcripts is also increased in the presomitic mesoderm of PS1(−/−) embryos, while the level of Notch1 transcripts is unchanged, in contrast to a previous report (Wong et al., 1997, Nature 387, 288–292). These results provide direct evidence that PS1 controls neuronal differentiation in association with the downregulation of Notch signalling during neurogenesis.

A Synthetic Small Molecule That Induces Neuronal Differentiation of Adult Hippocampal Neural Progenitor Cells

2006 ◽  
Vol 45 (4) ◽  
pp. 591-593 ◽  
Author(s):  
Masaki Warashina ◽  
Kyung Hoon Min ◽  
Tomoko Kuwabara ◽  
Alexis Huynh ◽  
Fred H. Gage ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neuronal Differentiation ◽  
Small Molecule ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Synthetic Small Molecule

Clock genes regulate neurogenic transcription factors, including NeuroD1, and the neuronal differentiation of adult neural stem/progenitor cells

2009 ◽  
Vol 54 (5-6) ◽  
pp. 277-285 ◽  
Author(s):  
Tomomi Kimiwada ◽  
Mikako Sakurai ◽  
Hiroki Ohashi ◽  
Shunsuke Aoki ◽  
Teiji Tominaga ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Progenitor Cells ◽  
Neuronal Differentiation ◽  
Clock Genes ◽  
Neural Stem Progenitor Cells

A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo

Development ◽  
1999 ◽  
Vol 126 (6) ◽  
pp. 1211-1223 ◽  
Author(s):  
T.P. Yamaguchi ◽  
A. Bradley ◽  
A.P. McMahon ◽  
S. Jones
Keyword(s):  
Progenitor Cells ◽  
Primitive Streak ◽  
The Body ◽  
Loss Of Function ◽  
Proliferating Cells ◽  
Precise Control ◽  
Cellular Processes ◽  
Cell Proliferation And Differentiation ◽  
Primary Body ◽  
Multiple Structures

Morphogenesis depends on the precise control of basic cellular processes such as cell proliferation and differentiation. Wnt5a may regulate these processes since it is expressed in a gradient at the caudal end of the growing embryo during gastrulation, and later in the distal-most aspect of several structures that extend from the body. A loss-of-function mutation of Wnt5a leads to an inability to extend the A-P axis due to a progressive reduction in the size of caudal structures. In the limbs, truncation of the proximal skeleton and absence of distal digits correlates with reduced proliferation of putative progenitor cells within the progress zone. However, expression of progress zone markers, and several genes implicated in distal outgrowth and patterning including Distalless, Hoxd and Fgf family members was not altered. Taken together with the outgrowth defects observed in the developing face, ears and genitals, our data indicates that Wnt5a regulates a pathway common to many structures whose development requires extension from the primary body axis. The reduced number of proliferating cells in both the progress zone and the primitive streak mesoderm suggests that one function of Wnt5a is to regulate the proliferation of progenitor cells.

Sign in / Sign up

Export Citation Format

Share Document