Abstract
Contemporary regenerative therapies have introduced stem-like cells to replace damaged neurons in the visual system by recapitulating critical processes of eye development. The collective migration of neural stem cells is fundamental to retinogenesis and has been exceptionally well-studied using the fruit fly model of Drosophila Melanogaster. However, the migratory behavior of its retinal neuroblasts (RNBs) has been surprisingly understudied, despite being critical to retinal development in this invertebrate model. The current project developed a new microfluidic system to examine the collective migration of RNBs extracted from the developing visual system of Drosophila as a model for the collective motile processes of replacement neural stem cells. The system scales with the microstructure of the Drosophila optic stalk, which is a pre-cursor to the optic nerve, to produce signaling fields spatially comparable to in vivo RNB stimuli. Experiments used the micro-optic stalk system, or μOS, to demonstrate the preferred sizing and directional migration of collective, motile RNB groups in response to changes in exogenous concentrations of fibroblast growth factor (FGF), which is a key factor in development. Our data highlight the importance of cell-to-cell contacts in enabling cell cohesion during collective RNB migration and point to the unexplored synergy of invertebrate cell study and microfluidic platforms to advance regenerative strategies.
Highlights
Visual impairment is a global health challenge that affects growing numbers of aging and mature adults each year [1,2,3]
The optic nerve is central to vision, and it is developmentally preceded by a microscale structure called the optic stalk, which enables axonal targeting from the brain to the developing eye [7]
Contemporary knowledge of eye formation has been largely derived from studies of the developing visual system of Drosophila Melanogaster
Summary
Visual impairment is a global health challenge that affects growing numbers of aging and mature adults each year [1,2,3]. The optic nerve is central to vision, and it is developmentally preceded by a microscale structure called the optic stalk, which enables axonal targeting from the brain to the developing eye [7] This critical neural communication is facilitated by the collective and highly coordinated migration of retinal neuroblasts (RNBs), or neural stem-like progenitors, along signaling gradients of motogenic and morphogenic factors [8,9]. Despite available spacing in the μOS for the migration of larger clustered RNB groups, RNBs were observed to disaggregate into smaller clusters of preferential size in response to changes in exogenous FGF concentration These data point to the underexplored significance of cell–cell contacts in collective RNB behaviors needed to advance stem cell-based therapies [43,44] and highlight synergistic opportunities to examine these interactions, mechanistically, via concurrent genetic manipulation and controlled extracellular stimuli
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