Morphological study of embryonic Chd8^+/- mouse brains using light-sheet microscopy.

Area of Science:

• Neurodevelopmental Biology
• Genetics
• Developmental Neuroscience

Background:

• Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with poorly understood genetic underpinnings.
• CHD8 is a significant risk gene associated with ASD.
• Heterozygous Chd8 loss-of-function in mice has been linked to early postnatal macrocephaly.

Purpose of the Study:

• To investigate early embryonic brain alterations in Chd8 haploinsufficiency.
• To identify measurable changes in brain morphology during early development.

Main Methods:

• Light-sheet fluorescence microscopy was used to image N-cadherin stained and optically cleared brains.
• Brains from Chd8+/- and wild-type mice at embryonic day 12.5 (E12.5) were analyzed.
• Detailed morphometric characterization of embryonic brain shapes and cortical neuroepithelial apical architecture was performed.

Main Results:

• No significant expansion of the forebrain and midbrain was observed at E12.5 in Chd8+/- mice.
• A trend towards decreased lateral ventricular sphericity was detected.
• An increased intraocular distance was found in Chd8+/- embryonic brains compared to controls.

Conclusions:

• Early embryonic brain development in Chd8 haploinsufficiency may exhibit subtle morphometric changes.
• High-resolution microscopy and multi-scale morphometric analyses are valuable tools for studying Chd8-related neurodevelopmental alterations.
• Further research is needed to understand the etiology and cellular basis of Chd8 haploinsufficiency.