Intertissue mechanical interactions shape the olfactory circuit in zebrafish

Abstract

While the chemical signals guiding neuronal migration and axon elongation have been extensively studied, the influence of mechanical cues on these processes remains poorly studied in vivo. Here, we investigate how mechanical forces exerted by surrounding tissues steer neuronal movements and axon extension during the morphogenesis of the olfactory placode in zebrafish. We mainly focus on the mechanical contribution of the adjacent eye tissue, which develops underneath the placode through extensive evagination and invagination movements. Using quantitative analysis of cell movements and biomechanical manipulations, we show that the developing eye exerts lateral traction forces on the olfactory placode through extracellular matrix, mediating proper morphogenetic movements and axon extension within the placode. Our data shed new light on the key participation of intertissue mechanical interactions in the sculpting of neuronal circuits.

Self-assembly of cellular neighborhoods converts stochastic signaling into sustained olfactory neurogenesis

“…Our targeted manipulations of RA levels suggest that RA production and diffusion from the eye acts as a critical pro-neurogenic influence on the composition and function of neurogenic neighborhoods. Interestingly, mechanical interactions between the developing eye and OE were recently shown to affect OE morphology 49 , which, together with our results, indicate significant mechanochemical interplay between the developing eye and nose. Sharp changes in Notch and RA signaling have been previously shown to attenuate noise in signal transduction resulting from stochastic variation and fluctuations in gene expression across space and time 4,5,28 .…”

Retina organoids: Window into the biophysics of neuronal systems

“…119 Ablation of Müller Glia cells in the zebrafish retina revealed their role as mechanosensitive springs holding the retina together in a compressive way. 129 Recently, the role of mechanical interaction of the developing eye field with the adjacent tissue has been probed in vivo 53 with the finding, that a mechanical contact of the forming optics vesicle to the adjacent tissue is required for proper development. Beyond mechanical manipulation, the technology has been used to characterize neuronal circuits in the zebrafish brain 130 and has revealed that the mechanosensitive ion channel Piezo1 also controls neuron regeneration.…”

“…As a result, the connection between optic vesicle and underlying surface ectoderm has identified as crucial for optics cup morphogenesis, raising the question how external mechanical signals from other tissues are required for proper retina development. 42,[53][54][55] There are several benefits of mapping cell-level models onto continuum descriptions. One benefit is experimental testing of models.…”

“…Recent in vivo experiments indicate the requirement of a mechanical coupling between the optic vesicle and the adjacent tissue. 53 This mechanical link is established via the extracellular matrix (ECM) and is crucial for the proper formation of neuronal connections. 42,[53][54][55] In RO protocols, a direct mechanical impact is implemented, e.g.…”

“…53 This mechanical link is established via the extracellular matrix (ECM) and is crucial for the proper formation of neuronal connections. 42,[53][54][55] In RO protocols, a direct mechanical impact is implemented, e.g. via the excision of the optic vesicle, 6,7,40 or the attachment of the embryoid body (EBs) onto planar substrates.…”