Biology subjects

Nerli, E.

Publications and source records attributed to Nerli, E..

6 recordsLinked to original sources

bioRxiv2025

Spatiotemporal Coordination of Guidance Cues Directs Multipolar Migration During Retinal Lamination

Multipolar migration is a conserved neuronal migration mode in the developing brain, enabling emerging neurons to navigate crowded environments and reach precise laminar positions. Yet how these cells interpret external cues to guide their migration remains unclear. We investigate this question in the developing vertebrate retina using horizontal cells as a model. Combining transcriptomics, targeted CRISPR screening, and live imaging, we reveal the spatiotemporal guidance system underlying horizontal cell lamination: repulsive Slit1b/2-Robo2 signaling in the amacrine cell layer is essential to initiate apical horizontal cell migration, while attractive Neurturin-Gfr1 signaling from photoreceptors fine-tunes final positioning beneath the photoreceptor layer. Disruption of these pathways causes basal retention of horizontal cells, highlighting the importance of spatially coordinated signaling for proper lamination and functional retinal circuitry. Our results uncover how positional signals and tissue architecture cooperate to achieve neuronal precision, an organizing principle likely relevant across the developing central nervous system.

developmental biology↗

bioRxiv2025

GEQO biosensors for absolute analyte quantification in single cells

Genetically encoded fluorescent biosensors are widely used to monitor small molecule and ion levels in living cells. Quantitative FRET and FLIM sensors and highly sensitive intensiometric sensors have been developed for many analytes. Notwithstanding notable advances over the last years, a universal high-performance sensor design for absolute quantification that does not require specialized equipment has yet to be developed. We here report the GEQO platform of quantitative biosensors featuring calcium, ATP, cAMP, and organelle-specific variants. We used GEQO sensors to follow calcium and cAMP transients in immortalised cells, human pancreatic progenitor cells, and zebrafish embryos. We show that GEQO-based absolute quantification allows to account for analyte buffering and retains information in time trace data lost during relative quantification. GEQO biosensors will enable quantitative analyte measurements across a wide range of imaging platforms, a key prerequisite for diagnostic applications and quantitative approaches in basic cell biology.

cell biology↗

bioRxiv2025

Injury-induced electrochemical coupling triggers regenerative cell proliferation

Organ injury triggers non-neuronal electric currents essential for regeneration. Yet, the mechanisms by which electrical signals are generated, sensed and transmitted upon damage to promote organ growth remain unclear. Here, we uncover that organ regeneration relies on dynamic electrochemical coupling between tissue-wide depolarization and intracellular proliferative signalling. By sub-second live imaging of injured zebrafish larval fins, we identify events across timescales: a millisecond tissue depolarization gradient, followed by seconds-persistent intracellular Calcium responses. Subsequently within one hour, Voltage Sensing Phosphatase activity translates depolarisation into proliferation. Connecting these timescales with an electro-diffusive model showed that ionic fluxes and electric potential become coupled in the fins interstitial space, enabling organ-wide signal spreading. Our work reveals the coupling between fast electrical signals and slower intracellular signalling, ensuring organ regeneration.

biophysics↗

bioRxiv2022

Deterministic and probabilistic fate decisions co-exist in a single retinal lineage

Correct nervous system development depends on the timely differentiation of progenitor cells into neurons. While the output of progenitor differentiation is well investigated at the population and clonal level, the possibilities and constraints for fate decisions of specific progenitors over development are less explored. Particularly little is known about their variability and competence plasticity. To fill this gap, we here use long-term live imaging to follow the outcome of progenitor divisions in the zebrafish retina. We find that neurogenic Atoh7 expressing progenitors produce different neuronal types over development with time-dependent probabilities. Interestingly, deterministic and probabilistic fate decisions co-exist in the same lineage. While interference with the deterministic fate affects lineage progression, interference with fate probabilities of the stochastic lineage branch results in a broader range of fate possibilities than seen in controls. When tissue development is challenged, Atoh7 expressing progenitors can produce any neuronal type, arguing against the concept of fixed competence windows. Stochastic modelling of fate probabilities in challenged conditions revealed a simple gene regulatory network able to recapitulate the observed competence changes during development. Based on our results, we postulate that fate plasticity could be involved in robust retinal development, a concept possibly applicable to other tissues.

developmental biology↗

bioRxiv2021

Bidirectional neuronal migration coordinates retinal morphogenesis bypreventing spatial competition

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.

developmental biology↗

bioRxiv2020

Asymmetric neurogenic commitment of retinal progenitors is regulated via the Notch endocytic pathway

During brain development, progenitor cells need to balance proliferation and differentiation in order to generate different neurons in the correct numbers and proportions. Currently, the patterns of multipotent progenitors’ division that lead to neurogenic entry and the factors that regulate them are not fully understood. We here use the zebrafish retina to address this gap, exploiting the possibilities for quantitative live-imaging. We show that early neurogenic progenitors arise from asymmetric divisions. Notch regulates this asymmetry as when inhibited, symmetric divisions producing two neurogenic progenitors occur. Surprisingly, Notch does not act through an apicobasal activity gradient as previously suggested but through asymmetric inheritance of Sara-positive endosomes. Further, the resulting neurogenic progenitors show cell biological features different from multipotent progenitors, raising the possibility that an intermediate state of progenitors exists in the retina. Our study thus opens new insights into the regulation of proliferative and differentiative events during central nervous system development.Competing Interest StatementThe authors have declared no competing interest.View Full Text

developmental biology↗