Biology subjects

Lahne, M.

Publications and source records attributed to Lahne, M..

3 recordsLinked to original sources

bioRxiv2026

Glia regulate local retinoic acid levels to specify neuronal specialisation for high-acuity vision

Neurons of the same type can be differentially tuned to perform distinct functional roles, yet how such specialisation arises during development remains poorly understood. Here, we show that in the zebrafish retina, heterogeneity within a single glial population generates local gradients of retinoic acid (RA) signalling that fine-tune neural function within a single neuronal type. The acute zone (AZ), a ventro-temporal region of the retina, is specialised for prey capture in the upper frontal visual field. In this region, UV cones exhibit enhanced light sensitivity through elongation of their outer segments (OS), the cellular compartment responsible for phototransduction. We found that cyp26 genes, which encode RA-degrading enzymes, are expressed in Muller glia in a region-specific manner, and that this expression pattern closely matches the spatial variation in cone OS length. Inhibition of Cyp26 activity prevented OS elongation in the AZ. This effect is mediated by RA signalling, as direct activation of RA receptors using RAR agonists similarly reduced OS length in this region. Notably, inhibition of Cyp26 predominantly activated RA signalling in Muller glia rather than in cones, indicating that RA signalling regulates cone OS length in a cell-non-autonomous manner via Muller glia. Consistent with this model, blocking Muller glia genesis abolished cone specialisation across all regions of the developing retina. Together, these findings identify Muller glia as key regulators of cone functional specialisation through the spatial control of RA signalling.

neuroscience↗

bioRxiv2022

Unique functions of two overlapping PAX6 retinal enhancers

Enhancers play a critical role in development by precisely modulating spatial, temporal, and cell type-specific gene expression. Sequence variants in enhancers have been implicated in disease, however establishing the functional consequences of these variants is challenging due to a lack of understanding of precise cell types and developmental stages where the enhancers are normally active. PAX6 is the master regulator of eye development, and has a regulatory landscape containing multiple enhancers driving expression in the eye. Whether these enhancers perform additive, redundant, or distinct functions is unknown. Here we describe the precise cell types and regulatory activity of two PAX6 retinal enhancers, HS5 and NRE. Using a unique combination of live imaging and single-cell RNA sequencing in dual enhancer-reporter zebrafish embryos, we find significant differences in the spatiotemporal activity of these enhancers, and show that HS5 and NRE are active in distinct cell types of the developing retina. Our results show that although overlapping, these enhancers have distinct activities in different cell types and therefore likely non-redundant functions. This work demonstrates that unique cell type-specific functions can be uncovered for apparently similar enhancers when investigated at high resolution in vivo.

genetics↗

bioRxiv2019

Comparative transcriptomic and epigenomic analysis identifies key regulators of injury response and neurogenic competence in retinal glia

Injury induces retinal Muller glia of cold-blooded, but not mammalian, vertebrates to regenerate neurons. To identify gene regulatory networks that control neuronal reprogramming in retinal glia, we comprehensively profiled injury-dependent changes in gene expression and chromatin accessibility in Muller glia from zebrafish, chick and mice using bulk RNA-Seq and ATAC-Seq, as well as single-cell RNA-Seq. Cross-species integrative analysis of these data, together with functional validation, identified evolutionarily conserved and species-specific gene networks controlling glial quiescence, gliosis and neurogenesis. In zebrafish and chick, transition from the resting state to gliosis is essential for initiation of retinal regeneration, while in mice a dedicated network suppresses neurogenic competence and restores quiescence. Selective disruption of NFI family transcription factors, which maintain and restore quiescence, enables Muller glia to proliferate and generate neurons in adult mice following retinal injury. These findings may aid in the design of cell-based therapies aimed at restoring retinal neurons lost to degenerative disease. Summary sentenceThis study identifies gene regulatory networks controlling proliferative and neurogenic competence in retinal Muller glia.

neuroscience↗