stimulating-analyzing-adult-neurogenesis-drosophila-central

Stimulating and Analyzing Adult Neurogenesis in the <em>Drosophila</em> Central Brain

The molecular and cellular mechanisms underlying neurogenesis in response to disease or injury are not well understood. However, understanding these ...

University of Wisconsin-Madison, School of Medicine and Public Health

A screen for neuroprotective genes in  led to the identification of a mutation that causes extreme, progressive loss of adult brain neuropil in conjunction with massive brain overgrowth. We mapped the mutation to the  () locus, which encodes a tripartite motif-NCL-1, HT2A, and LIN-41 (TRIM-NHL) RNA-binding protein with established roles limiting stem cell proliferation in developing brain and ovary. However, a neuroprotective role for  in the adult  brain has not been described previously. The new allele,  ( ), carries a mutation in the coiled-coil domain of the TRIM motif, and is temperature-sensitive. We demonstrate that mRNA and protein levels of neural stem cell genes are increased in heads of adult  mutants and that the over-proliferation phenotype initiates prior to adult eclosion. We also report that disruption of an uncharacterized gene coding for a presumptive prolyl-4-hydroxylase strongly enhances the over-proliferation and neurodegeneration phenotypes. Together, our results reveal an unexpected role for  that could be relevant to human cancer and neurodegenerative diseases.

A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in Adult .

 provides a powerful genetic model system in which to investigate the molecular mechanisms underlying neurodegenerative diseases. In this review, we discuss recent progress in  modeling Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis (ALS), Huntington's Disease, Ataxia Telangiectasia, and neurodegeneration related to mitochondrial dysfunction or traumatic brain injury. We close by discussing recent progress using  models of neural regeneration and how these are likely to provide critical insights into future treatments for neurodegenerative disorders.

Modeling Neurodegenerative Disorders in .

Neurodegenerative diseases such as Alzheimer's and Parkinson's currently affect ∼25 million people worldwide (Erkkinen et al. 2018). The global incidence of traumatic brain injury (TBI) is estimated at ∼70 million/year (Dewan et al. 2018). Both neurodegenerative diseases and TBI remain without effective treatments. We are utilizing adult Drosophila melanogaster to investigate the mechanisms of brain regeneration with the long term goal of identifying targets for neural regenerative therapies. We specifically focused on neurogenesis, i.e. the generation of new cells, as opposed to the regrowth of specific subcellular structures such as axons. Like mammals, Drosophila have few proliferating cells in the adult brain. Nonetheless, within 24 hours of a Penetrating Traumatic Brain Injury (PTBI) to the central brain, there is a significant increase in the number of proliferating cells. We subsequently detect both new glia and new neurons and the formation of new axon tracts that target appropriate brain regions. Glial cells divide rapidly upon injury to give rise to new glial cells. Other cells near the injury site upregulate neural progenitor genes including asense and deadpan and later give rise to the new neurons. Locomotor abnormalities observed after PTBI are reversed within two weeks of injury, supporting the idea that there is functional recovery. Together, these data indicate that adult Drosophila brains are capable of neuronal repair. We anticipate that this paradigm will facilitate the dissection of the mechanisms of neural regeneration and that these processes will be relevant to human brain repair.

Article	Year
A Novel Mutation in Brain Tumor Causes Both Neural Over-Proliferation and Neurodegeneration in Adult . G3 (Bethesda, Md.)\| PubMed ID: 30126833	2018
Modeling Neurodegenerative Disorders in . International journal of molecular sciences\| PubMed ID: 32357532	2020
Neurogenesis in the adult Drosophila brain. Genetics\| PubMed ID: 34117750	2021

Grace Boekhoff-Falk

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