What the fruit fly can tell us about autosomal recessive primary microcephaly
Shalini Chakraborty1, Steven Florez1, Todd Schoborg1
1Department of Molecular Biology, University of Wyoming, Laramie, WY USA.
Abstract:
Three decades of research aimed at understanding the basis for autosomal recessive primary microcephaly (MCPH), a human clinical disorder defined by a significant reduction in head and brain size, has uncovered a suite of ~30 genes that participate in this process. Work in both vertebrate and invertebrate model systems have been instrumental in attempting to link MCPH gene function to the brain growth phenotype. However, we still lack definitive evidence as to what these functions are for many of these genes. In this review, we summarize recent work in Drosophila aimed at overcoming these limitations in our knowledge of MCPH gene function that may be applicable to humans. We discuss the clinical features of MCPH, parallels between human and Drosophila neurogenesis modes with a particular focus on the fly optic lobe, and highlight four of the most well-studied Drosophila MCPH orthologs: abnormal spindle (asp)/MCPH5, Microcephalin/MCPH1, WD Repeat-Containing Protein 62 (Wdr62)/MCPH2, and Ankryin Repeat-and LEM Domain- Containing Protein 2 (ANKLE2)/MCPH16. We focus on the multifunctional roles for these proteins that may underlie the microcephaly phenotype and advocate for the use of flies as a relevant model for human MCPH.
Insights
Research using fruit flies (Drosophila) investigates genes causing autosomal recessive primary microcephaly (MCPH), a disorder of reduced head and brain size. This study highlights fly models for understanding human MCPH gene functions and neurodevelopment.
Area of Science:
- Developmental Biology
- Genetics
- Neuroscience
Background:
- Autosomal recessive primary microcephaly (MCPH) is a human disorder characterized by significantly reduced head and brain size.
- Approximately 30 genes have been linked to MCPH, but their precise functions in brain development remain largely unknown.
- Previous research utilized model systems to connect MCPH gene function to brain growth phenotypes, yet definitive evidence is lacking for many genes.
Purpose of the Study:
- To review recent findings from *Drosophila* research on MCPH gene function.
- To explore the applicability of *Drosophila* models to understanding human MCPH.
- To identify conserved neurogenesis mechanisms and MCPH gene roles between humans and *Drosophila*.
Main Methods:
- Comparative analysis of human and *Drosophila* neurogenesis, focusing on the optic lobe.
- Review of studies investigating the function of key *Drosophila* MCPH orthologs.
- Examination of the multifunctional roles of selected MCPH proteins in *Drosophila* models.
Main Results:
- Identified parallels between human and *Drosophila* neurogenesis, particularly in the optic lobe.
- Highlighted four well-studied *Drosophila* MCPH orthologs: asp/MCPH5, Microcephalin/MCPH1, Wdr62/MCPH2, and ANKLE2/MCPH16.
- Emphasized the multifunctional roles of these proteins potentially contributing to the microcephaly phenotype.
Conclusions:
- *Drosophila* serves as a relevant and powerful model system for studying human MCPH.
- Understanding the conserved functions of MCPH genes in flies can elucidate their roles in human brain development.
- Further research in *Drosophila* is crucial for deciphering the genetic basis of microcephaly.
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