Modeling Williams syndrome from a neurodevelopmental perspective: recent advances, model-based translational insights...

Area of Science:

• Genetics
• Neuroscience
• Developmental Biology

Background:

• Williams syndrome (WS) is a genetic disorder caused by a chromosome 7q11.23 microdeletion.
• WS is characterized by cardiovascular anomalies, distinct facial features, and neurodevelopmental issues like hypersociability and cognitive impairment.

Purpose of the Study:

• To review recent advancements in modeling Williams syndrome, focusing on neurodevelopmental aspects.
• To explore the utility of animal models and organoids in understanding WS mechanisms and potential therapies.

Main Methods:

• A narrative review of publications identified through PubMed/MEDLINE searches.
• Keywords included "Williams syndrome," genetic regions, neurodevelopmental terms, and specific genes and modeling techniques like organoids and induced pluripotent stem cells (iPSCs).

Main Results:

• Mouse models, including multigene deletion and single-gene knockout strains, replicate key WS neurodevelopmental phenotypes.
• Forebrain organoids derived from patients or generated via gene editing offer human-specific insights into neural progenitor dynamics and synaptic function.

Conclusions:

• Animal models and forebrain organoids have significantly advanced mechanistic understanding and translational research for WS.
• Further integration of these models with advanced technologies is crucial for biomarker discovery and developing mechanism-based therapies for WS.