Microcephaly is caused by a depletion in neural progenitor cells (NPCs). This depletion is caused by a mutation in the centrosome genes, and it occurs while the brain is still developing.
Researchers know that the depletion of NPS is related to TP53 related cell death. What researchers haven’t known (until now) is how the TP53 is first activated.
These researchers found that mitotic delays were caused by centrosome loss. These delays prevented the growth of cells by activating TP53, USP28, and 53BPI. In other words, centrosome defects were the root of it all.
Together, TP53, USP28, and 53BPI have been called the mitotic surveillance pathway. There is still more to learn, as there always is. But, this study has found that mutated centrosome genes lead to microcephaly due to their ability to delay mitosis. Additionally, these genes activate the mitotic surveillance pathway while the brain is still developing.
Due to this, the team believes that by inactivating the mitotic surveillance pathway, even after delayed mitosis has occurred, they could prevent further cell death by focusing on this particular pathway instead of on the centrosome defects themselves.
This investigation needs further inquiry, but researchers are hopeful about their increased understanding of the pathway of this rare disease. You can read the full results of the study, and what it may mean for future research here.