Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Pleiotropy01:33

Pleiotropy

41.0K
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
41.0K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

KCTD3 deficiency disrupts axon initial segment organization and neurite outgrowth in a neurodevelopmental disorder mouse model.

Communications biology·2026
Same author

A case of Incontinentia Pigmenti associated with concurrent <i>IKBKG/NEMO</i> and <i>MED13L</i> mutations.

Frontiers in medicine·2026
Same author

Structural variant discovery and diagnostic impact in rare diseases from short-read and long-read sequencing.

medRxiv : the preprint server for health sciences·2026
Same author

Global Socioeconomic Context and Brain Ageing in Epilepsy: an ENIGMA-Epilepsy study.

medRxiv : the preprint server for health sciences·2026
Same author

De novo EHMT2 variants cause an autosomal dominant EHMT2-related Kleefstra syndrome via loss of G9a methyltransferase activity.

Nature communications·2026
Same author

Expanding the ABCA2-associated neurodevelopmental phenotype.

HGG advances·2026

Related Experiment Video

Updated: Sep 4, 2025

Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
07:43

Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders

Published on: May 12, 2015

11.4K

Variant-specific changes in RAC3 function disrupt corticogenesis in neurodevelopmental phenotypes.

Marcello Scala1,2,3, Masashi Nishikawa3, Hidenori Ito3

  • 1Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.

Brain : a Journal of Neurology
|July 19, 2022
PubMed
Summary
This summary is machine-generated.

Genetic variants in RAC3 cause a rare neurodevelopmental disorder. These RAC3 gene mutations lead to brain malformations and developmental delays in affected individuals.

Keywords:
RAC3axon guidancebrain developmentneuronal migrationsmall GTPase

More Related Videos

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

13.8K
A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
08:22

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

Published on: December 1, 2017

8.7K

Related Experiment Videos

Last Updated: Sep 4, 2025

Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders
07:43

Immunohistochemical Visualization of Hippocampal Neuron Activity After Spatial Learning in a Mouse Model of Neurodevelopmental Disorders

Published on: May 12, 2015

11.4K
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

13.8K
A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
08:22

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

Published on: December 1, 2017

8.7K

Area of Science:

  • Genetics
  • Neuroscience
  • Developmental Biology

Background:

  • Variants in the RAC3 gene are linked to a rare neurodevelopmental disorder characterized by brain anomalies and facial dysmorphism.
  • RAC3 is a small GTPase crucial for actin cytoskeleton regulation and intracellular signaling.

Purpose of the Study:

  • To investigate the clinical and pathophysiological significance of de novo RAC3 variants in a cohort of unrelated individuals with neurodevelopmental abnormalities.
  • To elucidate the mechanisms by which RAC3 variants impact cortical neuron development.

Main Methods:

  • Clinical evaluation and brain MRI of 10 unrelated participants with global psychomotor delay and other neurodevelopmental features.
  • Identification and characterization of eight distinct de novo RAC3 variants.
  • In vitro biochemical assays to assess variant activity and effector binding.
  • In utero electroporation in mouse embryos to study the effects of RAC3 variants on cortical neuron morphology and migration.

Main Results:

  • The cohort presented with global psychomotor delay, hypotonia, behavioral issues, seizures, and complex brain malformations.
  • Eight distinct de novo RAC3 variants were identified, including six novel ones.
  • In vitro studies showed RAC3 variants have varying biochemical activity and effector affinities.
  • Expression of specific RAC3 variants in mouse brains caused defects in cortical neuron migration and morphology, with some defects being rescueable by targeting p21-activated kinase 1.

Conclusions:

  • RAC3 variants are associated with a spectrum of neurodevelopmental phenotypes and significant brain malformations.
  • Variant-specific mechanisms underlie the observed defects in cortical neuron development and migration.
  • These findings highlight the critical role of RAC3 in human brain development.