Collective behaviors of Drosophila-derived retinal progenitors in controlled microenvironments.

Caroline D Pena,Tadmiri Venkatesh,Maribel Vazquez,Stephanie Zhang,Miles Markey,Jongyoon Han

doi:10.1371/journal.pone.0226250

Caroline D Pena, Tadmiri Venkatesh + Show 4 more

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https://doi.org/10.1371/journal.pone.0226250

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Abstract

Collective behaviors of retinal progenitor cells (RPCs) are critical to the development of neural networks needed for vision. Signaling cues and pathways governing retinal cell fate, migration, and functional organization are remarkably conserved across species, and have been well-studied using Drosophila melanogaster. However, the collective migration of heterogeneous groups of RPCs in response to dynamic signaling fields of development remains incompletely understood. This is in large part because the genetic advances of seminal invertebrate models have been poorly complemented by in vitro cell study of its visual development. Tunable microfluidic assays able to replicate the miniature cellular microenvironments of the developing visual system provide newfound opportunities to probe and expand our knowledge of collective chemotactic responses essential to visual development. Our project used a controlled, microfluidic assay to produce dynamic signaling fields of Fibroblast Growth Factor (FGF) that stimulated the chemotactic migration of primary RPCs extracted from Drosophila. Results illustrated collective RPC chemotaxis dependent on average size of clustered cells, in contrast to the non-directional movement of individually-motile RPCs. Quantitative study of these diverse collective responses will advance our understanding of retina developmental processes, and aid study/treatment of inherited eye disease. Lastly, our unique coupling of defined invertebrate models with tunable microfluidic assays provides advantages for future quantitative and mechanistic study of varied RPC migratory responses.

Highlights

The collective migration of retinal progenitor cells (RPCs) is fundamental to development, where heterogeneous RPCs of neuronal and glial lineages assemble the signaling networks critical for vision [1,2]
Collective behaviors of retinal progenitor cells during development Contemporary knowledge of the visual system has been significantly advanced through genetic study of retinal development in Drosophila Melanogaster [2,15,22]
Extensive scrutiny of this seminal invertebrate model has illustrated that vision-critical processes are highly-conserved across species, and occur within retinal architecture that is developed through the precise, collective chemotaxis of its varied progenitor groups [12,13,50,51]

Summary

Introduction

The collective migration of retinal progenitor cells (RPCs) is fundamental to development, where heterogeneous RPCs of neuronal and glial lineages assemble the signaling networks critical for vision [1,2]. Microfluidic assays can significantly advance vision research by enabling quantitative study of the complex and poorly understood relationships between exogenous chemotactic fields and the collective RPC motility stimulated during retinogenesis [12,13,14]. Signaling cues governing cell migration in the developing visual system have been exceptionally well-studied using the invertebrate system of Drosophila melanogaster, or fruit fly [15,16,17,18]. Development of the compound eye requires the collective migration of heterogeneous RPC groups, i.e. both neuronal and glial progenitors, involving signaling pathways and mechanistic processes surprisingly analogous to vertebrate retinogenesis [19,23,24]. The combination of conserved pathways with significant genetic tools available, underscores Drosophila as a uniquely advantageous model with which to examine collective chemotactic responses of RPCs

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