Daughterless, the Drosophila orthologue of TCF4, is required for associative learning and maintenance of the synaptic proteome.

Autor:	Tamberg L; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia laura.tamberg@taltech.ee mari.palgi@taltech.ee., Jaago M; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia.; Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia., Säälik K; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia., Sirp A; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia., Tuvikene J; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia.; Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia., Shubina A; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia., Kiir CS; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia., Nurm K; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia., Sepp M; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia., Timmusk T; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia.; Protobios LLC, Mäealuse 4, Tallinn 12618, Estonia., Palgi M; Department of Chemistry and Biotechnology, Tallinn University of Technology, Akadeemia tee 15, Tallinn 12618, Estonia laura.tamberg@taltech.ee mari.palgi@taltech.ee.
Jazyk:	angličtina
Zdroj:	Disease models & mechanisms [Dis Model Mech] 2020 Jul 30; Vol. 13 (7). Date of Electronic Publication: 2020 Jul 30.
DOI:	10.1242/dmm.042747
Abstrakt:	Mammalian transcription factor 4 (TCF4) has been linked to schizophrenia and intellectual disabilities, such as Pitt-Hopkins syndrome (PTHS). Here, we show that similarly to mammalian TCF4, fruit fly orthologue Daughterless (Da) is expressed widely in the Drosophila brain. Furthermore, silencing of da , using several central nervous system-specific Gal4 driver lines, impairs appetitive associative learning of the larvae and leads to decreased levels of the synaptic proteins Synapsin (Syn) and Discs large 1 (Dlg1), suggesting the involvement of Da in memory formation. Here, we demonstrate that Syn and dlg1 are direct target genes of Da in adult Drosophila heads, as Da binds to the regulatory regions of these genes and the modulation of Da levels alter the levels of Syn and dlg1 mRNA. Silencing of da also affects negative geotaxis of the adult flies, suggesting the impairment of locomotor function. Overall, our findings suggest that Da regulates Drosophila larval memory and adult negative geotaxis, possibly via its synaptic target genes Syn and dlg1 These behavioural phenotypes can be further used as a PTHS model to screen for therapeutics.This article has an associated First Person interview with the first author of the paper. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2020. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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