Reference Report

Reference
Citation	Hazelett, D.J., Chang, J.C., Lakeland, D.L., Morton, D.B. (2012). Comparison of Parallel High-Throughput RNA Sequencing Between Knockout of TDP-43 and Its Overexpression Reveals Primarily Nonreciprocal and Nonoverlapping Gene Expression Changes in the Central Nervous System of Drosophila. G3 (Bethesda) 2(7): 789--802. (Export to RIS)
FlyBase ID	FBrf0219102
Publication Type	Research paper
PubMed ID	22870402
PubMed Abstract	The human Tar-DNA binding protein, TDP-43, is associated with amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. TDP-43 contains two conserved RNA-binding motifs and has documented roles in RNA metabolism, including pre-mRNA splicing and repression of transcription. Here, using Drosophila melanogaster as a model, we generated loss-of-function and overexpression genotypes of Tar-DNA binding protein homolog (TBPH) to study their effect on the transcriptome of the central nervous system (CNS). By using massively parallel sequencing methods (RNA-seq) to profile the CNS, we find that loss of TBPH results in widespread gene activation and altered splicing, much of which are reversed by rescue of TBPH expression. Conversely, TBPH overexpression results in decreased gene expression. Although previous studies implicated both absence and mis-expression of TDP-43 in ALS, our data exhibit little overlap in the gene expression between them, suggesting that the bulk of genes affected by TBPH loss-of-function and overexpression are different. In combination with computational approaches to identify likely TBPH targets and orthologs of previously identified vertebrate TDP-43 targets, we provide a comprehensive analysis of enriched gene ontologies. Our data suggest that TDP-43 plays a role in synaptic transmission, synaptic release, and endocytosis. We also uncovered a potential novel regulation of the Wnt and BMP pathways, many of whose targets appear to be conserved.
DOI	10.1534/g3.112.002998
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Secondary IDs
Language of Publication	English
Additional Languages of Abstract
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Parent Publication
Publication Type	Journal
Abbreviation	G3 (Bethesda)
Title	G3 : genes - genomes - genetics
Publication Year
ISBN/ISSN	2160-1836
Data from Reference
Aberrations (1)
	Df(2R)or-BR11
Alleles (8)
	Scer\GAL4^D42 Scer\GAL4^TBPH.PH TBPH^A1 TBPH^G2 TBPH^KG08578 TBPH^Scer\UAS.cHa TBPH^Δ23 TBPH^Δ142
Constructs (2)
	P{TBPH-GAL4.H} P{UAS-TBPH.H}
Genes (136)
	Acf1 Adar Amph AP-1γ Ark arm arr att-ORFA axo baz cac cact CadN CG1607 CG2747 CG3078 CG3308 CG3744 CG4080 CG4293 CG4400 CG5214 CG6051 CG6287 CG6509 CG6966 CG7028 CG8223 CG8726 CG9318 CG9705 CG9919 CG10011 CG10353 CG11399 CG11880 CG12084 CG13204 CG14322 CG14614 CG14764 CG15356 CG15628 CG15735 CG15822 CG17341 CG17754 CG31739 CG32479 CG33181 CG34113 CG34127 CG34353 CG34394 CG34449 CG42404 CG43729 chrb CkIIβ Clic CRMP cv-d dally dbo Ddc dlg1 dome dve Exn form3 futsch Glg1 H ham Hph htt InR l(1)G0289 l(3)05822 ltl mAcR-60C MAPk-Ak2 MED1 NaCP60E Nak Nap1 NetB nvy opa Pde9 Pdk1 Pex23 pgant2 pgant5 Pka-C1 Pkn PP2A-B' ppa Rab8 Rab35 Rala rb rok RpS15Aa S Sap-r sax Scer\GAL4 Sema-1b Sh skpA slmb smi35A Smox sno sns Socs16D spin spir ssp3 stck Su(dx) Su(var)3-9 Surf4 Synd tai tau TBPH Timp toc Trn twin UGP Unc-115a ush wts
Insertions (2)
	P{GawB}D42 P{SUPor-P}TBPH^KG08578
Natural transposons (1)
	P-element