C₂H₂-Type Zinc Finger Proteins in Brain Development, Neurodevelopmental, and Other Neuropsychiatric Disorders:...

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• Neurodevelopmental disorders (NDDs) involve intellectual disability, autism, and psychiatric issues, often linked to abnormal neural stem cell (NSC) function and gene regulation.
• C2H2-type zinc finger proteins (C2H2-ZNFs), the largest human transcription factor family, are increasingly implicated in NDD pathogenesis.

Purpose of the Study:

• To review the physiological roles of C2H2-ZNFs in brain development, particularly in NSCs.
• To elucidate the pathological implications of C2H2-ZNFs in various NDDs.
• To analyze the specific roles of poly-ZNFs and KRAB-ZNFs in NDDs.

Main Methods:

• Literature review of studies on C2H2-ZNFs, neurodevelopment, and NDDs.
• Analysis of C2H2-ZNF expression and function in brain physiology and pathology.
• Categorization of C2H2-ZNFs based on their involvement in different NDD types.

Main Results:

• C2H2-ZNFs are significantly represented in the brain (~10% of human members), playing key roles in neurogenesis and brain development.
• Specific C2H2-ZNF subclasses, poly-ZNFs and KRAB-ZNFs, show distinct associations with NDDs affecting brain structure and higher-order functions, respectively.
• These findings align with the evolutionary trajectory and functional specialization of C2H2-ZNFs.

Conclusions:

• C2H2-ZNFs are critical regulators in both normal brain development and the pathophysiology of NDDs.
• Understanding C2H2-ZNF functions offers potential therapeutic targets for NDDs.
• The distinct roles of C2H2-ZNF subclasses highlight their specialized contributions to complex brain functions and disorders.