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Published on: June 23, 2023
Understanding microcephaly through the study of centrosome regulation in Drosophila neural stem cells
Beverly V Robinson1, Victor Faundez1, Dorothy A Lerit1
1Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, U.S.A.
Abstract:
Microcephaly is a rare, yet devastating, neurodevelopmental condition caused by genetic or environmental insults, such as the Zika virus infection. Microcephaly manifests with a severely reduced head circumference. Among the known heritable microcephaly genes, a significant proportion are annotated with centrosome-related ontologies. Centrosomes are microtubule-organizing centers, and they play fundamental roles in the proliferation of the neuronal progenitors, the neural stem cells (NSCs), which undergo repeated rounds of asymmetric cell division to drive neurogenesis and brain development. Many of the genes, pathways, and developmental paradigms that dictate NSC development in humans are conserved in Drosophila melanogaster. As such, studies of Drosophila NSCs lend invaluable insights into centrosome function within NSCs and help inform the pathophysiology of human microcephaly. This mini-review will briefly survey causative links between deregulated centrosome functions and microcephaly with particular emphasis on insights learned from Drosophila NSCs.
Insights
Microcephaly, a condition of reduced head size, is linked to centrosome dysfunction. Studies in Drosophila neural stem cells (NSCs) offer key insights into human microcephaly causes.
Area of Science:
- Neurodevelopmental Biology
- Genetics
- Cell Biology
Background:
- Microcephaly is a severe neurodevelopmental disorder characterized by a small head circumference.
- Genetic and environmental factors, including Zika virus, can cause microcephaly.
- Many genes associated with heritable microcephaly are linked to centrosome function.
Purpose of the Study:
- To review the connection between disrupted centrosome function and microcephaly.
- To highlight insights gained from studying Drosophila neural stem cells (NSCs).
Main Methods:
- Literature review focusing on centrosome biology and microcephaly.
- Comparative analysis of conserved developmental pathways in humans and Drosophila.
- Examination of Drosophila NSCs to understand centrosome roles in neurogenesis.
Main Results:
- Centrosomes are crucial for neural stem cell proliferation and asymmetric cell division.
- Dysfunctional centrosomes impair neurogenesis, contributing to microcephaly.
- Drosophila NSCs provide a model to study the molecular mechanisms of microcephaly.
Conclusions:
- Disregulated centrosome function is a significant factor in microcephaly pathogenesis.
- Drosophila models are valuable for elucidating the cellular basis of human microcephaly.
- Further research into centrosome biology may reveal new therapeutic targets for microcephaly.
