Primary microcephaly: identification of new molecular mechanisms
A research team from the Department of Biology and Biotechnology Charles Darwin at Sapienza University of Rome and the Institute of Molecular Biology and Pathology of the National Research Council in Rome (CNR-IBPM) has conducted a study, published in the journal "Development", identifying new molecular mechanisms involved in autosomal recessive primary microcephaly (MCPH), a rare genetic disorder. MCPH is present from birth and is characterised by a marked reduction in head circumference and brain size, often associated with intellectual disability. “Using the fruit fly, Drosophila melanogaster, as a model organism, we discovered that two genes involved in this condition, ASPM and CENPJ, play a crucial role in maintaining cellular architecture and organising chromatin, the complex of proteins and DNA that makes up chromosomes.
“Our findings show that these microcephaly-associated proteins do not only control cell division but, through the regulation of chromatin organisation, may also influence gene expression, thereby contributing to cell survival and function, as well as to brain development itself,” says Laura Ciapponi, lecturer at Sapienza University of Rome and co-author of the study. In recent years, more than thirty genes associated with primary microcephaly have been identified. Many of these are involved in the formation of centrosomes, multiprotein complexes that are essential for organising the cytoskeleton—which gives cells their shape and structural support—and for the correct progression of cell division.
“This research highlights how certain alterations to the cytoskeleton and centrosomes can have much broader effects than previously understood. In fact, loss of ASPM and CENPJ function causes significant changes to the structure of the nuclear envelope and chromatin in developing brain cells, thereby compromising genome organisation and DNA stability,” adds Patrizia Somma, a researcher at CNR-IBPM and co-author of the study.
These findings contribute to a better understanding of the molecular mechanisms underlying brain development and open up new perspectives for the study and treatment of primary microcephaly, potentially paving the way for the development of future targeted therapeutic strategies.
The article has been selected by the journal "Development" for its ‘Research Highlights’ section, which will feature a dedicated piece on the study. The feature will also include an interview with Laura Ciapponi and first author Degisew Y. Mengistu in the ‘The people behind the paper’ section.
References: Mengistu D. Y., Marzullo M., Pellacani C., Marchetti M., Terribili M., Montivero Morales E., Somma M. P. and Ciapponi L. Microcephaly-associated genes asp and Sas4 influence chromatin organization and nuclear lamina structure in Drosophila melanogaster. Development (2026)
DOI: 10.1242/dev.205125
Further Information
Laura Ciapponi – Department of Biology and Biotechnology Charles Darwin