Gonçalves-Pimentel C, Mazaud D, Kottler B, Proelss S, Hirth F, Fanto M. A miRNA screen procedure identifies garz as an essential factor in adult glia functions and validates Drosophila as a beneficial 3Rs model to study glial functions and GBF1 biology. F1000Res. 2020 May 1;9:317. doi:
10.12688/f1000research.23154.2. PMID: 32595956; PMCID: PMC7309417.
Abstract:
"Invertebrate glia performs most of the key functions controlled by
mammalian glia in the nervous system and provides an ideal model for
genetic studies of glial functions. To study the influence of adult
glial cells in ageing we have performed a genetic screen in Drosophila
using a collection of transgenic lines providing conditional expression
of micro-RNAs (miRNAs). Here, we describe a methodological algorithm to
identify and rank genes that are candidate to be targeted by miRNAs
that shorten lifespan when expressed in adult glia. We have used four
different databases for miRNA target prediction in Drosophila but
find little agreement between them, overall. However, top candidate
gene analysis shows potential to identify essential genes involved in
adult glial functions. One example from our top candidates' analysis is gartenzwerg ( garz). We establish that garz
is necessary in many glial cell types, that it affects motor behaviour
and, at the sub-cellular level, is responsible for defects in cellular
membranes, autophagy and mitochondria quality control. We also verify
the remarkable conservation of functions between garz and its mammalian orthologue, GBF1, validating the use of Drosophila
as an alternative 3Rs-beneficial model to knock-out mice for studying
the biology of GBF1, potentially involved in human neurodegenerative
diseases."
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