Optogenetic approaches for understanding homeostatic and degenerative processes in Drosophila

Abstract

Many organs and tissues have an intrinsic ability to regenerate from a dedicated, tissue-specific stem cell pool. As organisms age, the process of self-regulation or homeostasis begins to slow down with fewer stem cells available for tissue repair. Tissues become more fragile and organs less efficient. This slowdown of homeostatic processes leads to the development of cellular and neurodegenerative diseases. In this review, we highlight the recent use and future potential of optogenetic approaches to study homeostasis. Optogenetics uses photosensitive molecules and genetic engineering to modulate cellular activity in vivo , allowing precise experiments with spatiotemporal control. We look at applications of this technology for understanding the mechanisms governing homeostasis and degeneration as applied to widely used model organisms, such as Drosophila melanogaster , where other common tools are less effective or unavailable.

Drosophila melanogaster as a model to study autophagy in neurodegenerative diseases induced by proteinopathies

“…Additionally, loss-of-function mutations or overexpression of genes can be easily obtained using CRISPR/Cas9 technology and commercially available sgRNA lines deposited at the Bloomington Stock Center ( Ewen-Campen et al, 2017 ; Zirin et al, 2022 ). More recently, novel optogenetic techniques have been successfully developed to study protein misfolding in vivo in the brain using Drosophila models of Alzheimer’s disease (AD), Parkinson’s disease (PD), and TDP-43/ALS ( Lim et al, 2021 ). The morphological defects induced by the expression of genes responsible for human PPs ( Figures 1A , B ) can be easily analyzed after their expression in Drosophila ( Figure 1C ) using ex vivo dissection of the entire larval or in adult-fly brains, using different techniques ranging from immunofluorescence to super resolution microscopy (SEM or TEM; Figure 1D ).…”

Wnt Signaling Rescues Amyloid Beta-Induced Gut Stem Cell Loss

“…We recently described an optogenetic method to study Aβ protein oligomerization in vivo in several model organisms [ 11 ]. Optogenetics refers to genes that are modified with a light responsive protein domain, allowing the spatial and temporal regulation of proteins [ 12 ]. Temporal and spatial control is achieved by light exposure of a specific wavelength, without the need to introduce other external agents [ 13 , 14 ].…”