Cellular Models and High-Throughput Screening for Genetic Causality of Intellectual Disability

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Intellectual disabilities (ID) are neurodevelopmental disorders (NDDs) with genetic origins.
• An emerging class of IDs is associated with Rho GTPases, specifically Ras-related C3 botulinum toxin substrate 1 (RAC1).
• Morphological aberrations in cellular models are a recognized hallmark of ID.

Purpose of the Study:

• To discuss the class of intellectual disabilities associated with RAC1.
• To review existing and novel cellular models for studying ID.
• To examine the progress and challenges in applying high-throughput screening (HTS) to neurological disorder research.

Main Methods:

• Review of established and novel cellular models for ID, including mouse and human primary cells.
• Exploration of reprogrammed or induced neurons as disease models.
• Analysis of high-throughput screening (HTS) methodologies in the context of neurological disorders.

Main Results:

• Cellular models, despite morphological aberrations, are crucial for understanding ID.
• Various cellular models, from primary cells to induced neurons, are available for ID research.
• HTS offers potential for biological insight but faces adoption challenges in the neurological disorder community.

Conclusions:

• RAC1-centric IDs represent a significant area within neurodevelopmental disorders.
• Advancements in cellular modeling and HTS are vital for dissecting the genetic basis of ID.
• Further integration of HTS methodologies is needed to accelerate discoveries in neurological disorder research.