Bidirectional neuronal migration coordinates retinal morphogenesis by preventing spatial competition

Abstract

While the design of industrial products is often optimized for the sequential assembly of single components, organismal development is hallmarked by the concomitant occurrence of tissue growth and organization. Often this means that proliferating and differentiating cells occur at the same time in a shared tissue environment that continuously changes. How cells adapt to architectural changes in order to prevent spatial interference remains unclear. To understand how cell movements important for growth and organization are orchestrated, we here study the emergence of photoreceptor neurons that occur during the peak of retinal growth using zebrafish, human tissue and human organoids. Quantitative imaging reveals that successful retinal morphogenesis depends on active bidirectional photoreceptor translocation. This leads to a transient transfer of the entire cell population away from the apical proliferative zone. This migration pattern is driven by distinct cytoskeletal machineries, depending on direction: microtubules are required for basal translocation, while actomyosin drives apical movement. Blocking photoreceptor translocation leads to apical overcrowding that hampers progenitor movements. Thus, photoreceptor migration is crucial to prevent competition for space and thereby allows concurrent tissue growth and lamination. This shows that neuronal migration, in addition to its canonical role in cell positioning, is involved in coordinating morphogenesis.

Fat3 acts through independent cytoskeletal effectors to coordinate asymmetric cell behaviors during polarized circuit assembly

“…Although defects in neuronal migration early in retinal development can have secondary effects on cell morphogenesis ( Rocha-Martins et al, 2021 ) or synapse localization ( Collin et al, 2020 ), we find that Fat3 acts through effectors that independently contribute to each of these important steps in AC development. For instance, a WIRS motif binds the WRC, which induces actin filament branching, whereas the Evh1 binding sites recruit Ena/VASP proteins, which promote actin filament elongation ( Bear and Gertler, 2009 ; Rottner et al, 2021 ).…”

Amoeboid-like migration ensures correct horizontal cell layer formation in the developing vertebrate retina

“…During long stretches of their migration, HCs follow unconventional tortuous migratory tracks while frequently alternating between radial (up and down) and tangential (lateral) routes. Such migration trajectories also set HCs apart from other emerging retinal neurons including PRs ( Rocha-Martins et al, 2021 ) and RGCs ( Icha et al, 2016a ) that display bipolar morphologies and remain constrained to radial migratory routes. While these neurons also undergo some deformations in the crowded retina, their migration success most likely does not depend on these deformations as they remain anchored to the tissue surface throughout their migration cycle.…”

“…Retinal neurons follow diverse and complex migratory modes and routes to reach their destinations ( Chow et al, 2015 ; Icha et al, 2016a , Amini et al, 2017 ; Amini et al, 2019 ; Rocha-Martins et al, 2021 ). However, parameters that ensure successful migration of diverse neuronal cell types in the complex and highly dynamic environment of the retina are only beginning to be understood ( Chow et al, 2015 ; Icha et al, 2016a , Amini et al, 2019 ).…”

Amoeboid-like neuronal migration ensures correct horizontal cell layer formation in the developing vertebrate retina

“…The copyright holder for this this version posted October 17, 2021. ; https://doi.org/10.1101/2021.10.15.464510 doi: bioRxiv preprint complex and highly dynamic environment are only beginning to be understood (Chow et al 2015, Icha et al 2016a, Amini et al 2019, Rocha-Martins et al 2021.…”

“…Retinal neurons follow diverse and complex migratory modes and routes to reach their destinations (Chow et al 2015, Icha et al 2016a, Amini, Rocha-Martins and Norden 2017, Amini, Labudina and Norden 2019, Rocha-Martins et al 2021. So far however, parameters that influence successful migration of the diverse neuron types in their complex and highly dynamic environment are only beginning to be understood (Chow et al 2015, Icha et al 2016a, Amini et al 2019, Rocha-Martins et al 2021.…”