Disruption of Aspm causes microcephaly with abnormal neuronal differentiation

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Mutations in the ASPM gene are linked to primary microcephaly, a condition characterized by reduced brain size.
• Understanding ASPM's role is crucial for elucidating the pathogenesis of microcephaly.

Purpose of the Study:

• To investigate the function of ASPM in brain development using a mouse model of human autosomal recessive primary microcephaly-5 (MCPH5).

Main Methods:

• Generated Aspm knock-out mice by flanking exons 2-3 with loxP sites for cre-recombinase mediated deletion.
• Analyzed adult and fetal brains using immunohistochemistry and morphometry.

Main Results:

• Aspm(-/-) mice exhibited smaller brains, particularly the cerebrum.
• Significant alterations in cortical layer thickness (thicker layer I, thinner layer VI) and reduced cortical plate thickness and cell number at E16.5 were observed.
• Increased expression of Tbr1 and Satb2 in the subplate of Aspm(-/-) mice.

Conclusions:

• ASPM is essential for the proliferation and differentiation of neural stem and progenitor cells.
• This Aspm gene loss model offers insights into the development of microcephaly, potentially linked to in utero teratogen exposure.