Comprehensive Characterization of the Complex lola Locus Reveals a Novel Role in the Octopaminergic Pathway via Tyramine Beta-Hydroxylase Regulation
File(s)
Published version
Author(s)
Dinges, Nadja
Morin, Violeta
Kreim, Nastasja
Southall, Tony D
Roignant, Jean-Yves
Type
Journal Article
Abstract
Longitudinals lacking (lola) is one of the most complex genes in Drosophila melanogaster, encoding up to 20 protein isoforms that include key transcription factors involved in axonal pathfinding and neural reprogramming. Most previous studies have employed loss-of-function alleles that disrupt lola common exons, making it difficult to delineate isoform-specific functions. To overcome this issue, we have generated isoform-specific mutants for all isoforms using CRISPR/Cas9. This enabled us to study specific isoforms with respect to previously characterized roles for Lola and to demonstrate a specific function for one variant in axon guidance via activation of the microtubule-associated factor Futsch. Importantly, we also reveal a role for a second variant in preventing neurodegeneration via the positive regulation of a key enzyme of the octopaminergic pathway. Thus, our comprehensive study expands the functional repertoire of Lola functions, and it adds insights into the regulatory control of neurotransmitter expression in vivo.
Date Issued
2017-12-05
Date Acceptance
2017-11-02
Citation
Cell Reports, 2017, 21 (10), pp.2911-2925
ISSN
2211-1247
Publisher
Elsevier
Start Page
2911
End Page
2925
Journal / Book Title
Cell Reports
Volume
21
Issue
10
Copyright Statement
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Sponsor
Wellcome Trust
Grant Number
104567/Z/14/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
AXON GUIDANCE GENE
NEURAL STEM-CELLS
DROSOPHILA-MELANOGASTER
LIFE-SPAN
PROTEIN
EXPRESSION
DOMAIN
DIFFERENTIATION
LOCOMOTION
DOPAMINE
Publication Status
Published