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Abstract
ARHGEF39 was previously implicated in developmental language disorder (DLD) via
a functional polymorphism that can disrupt post-transcriptional
regulation by microRNAs. ARHGEF39 is part of the family of Rho guanine
nucleotide exchange factors (RhoGEFs) that activate small Rho GTPases to
regulate a wide variety of cellular processes. However, little is known
about the function of ARHGEF39, or how its function might
contribute to neurodevelopment or related disorders. Here, we explore
the molecular function of ARHGEF39 and show that it activates the Rho
GTPase RHOA and that high ARHGEF39 expression in cell cultures leads to
an increase of detached cells. To explore its role in neurodevelopment,
we analyse published single cell RNA-sequencing data and demonstrate
that ARHGEF39 is a marker gene for proliferating neural
progenitor cells and that it is co-expressed with genes involved in cell
division. This suggests a role for ARHGEF39 in neurogenesis in the developing brain. The co-expression of ARHGEF39
with other RHOA-regulating genes supports RHOA as substrate of ARHGEF39
in neural cells, and the involvement of RHOA in neuropsychiatric
disorders highlights a potential link between ARHGEF39 and
neurodevelopment and disorder. Understanding the GTPase substrate,
co-expression network, and processes downstream of ARHGEF39
provide new avenues for exploring the mechanisms by which altered
expression levels of ARHGEF39 may contribute to neurodevelopment and
associated disorders.
Original language | English |
---|---|
Article number | 941494 |
Journal | Frontiers in Molecular Neuroscience |
Volume | 15 |
DOIs | |
Publication status | Published - 25 Jul 2022 |
Keywords
- Neuroscience
- ARHGEF39
- Rho GTPases
- RHOA
- Cell adhesion
- scRNA-seq
- Neural progenitor cells (NPCs)
- Cell division
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Dive into the research topics of 'ARHGEF39, a gene implicated in developmental language disorder, activates RHOA and is involved in cell de-adhesion and neural progenitor cell proliferation'. Together they form a unique fingerprint.Projects
- 1 Finished
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Sonja Vernes UKRI Future Leaders: Mammalian vocal communication as a model for human language; from genes and brains to behaviour
Vernes, S. (PI)
1/11/20 → 31/10/24
Project: Fellowship