Differentiation signals from glia are fine-tuned to set neuronal numbers during development
Abstract
Neural circuit formation and function require that diverse neurons are specified in appropriate numbers. Known strategies for controlling neuronal numbers involve regulating either cell proliferation or survival. We used the Drosophila visual system to probe how neuronal numbers are set. Photoreceptors from the eye-disc induce their target field, the lamina, such that for every unit eye there is a corresponding lamina unit (column). Although each column initially contains ~6 post-mitotic lamina precursors, only 5 differentiate into neurons, called L1-L5; the 'extra' precursor, which is invariantly positioned above the L5 neuron in each column, undergoes apoptosis. Here, we showed that a glial population called the outer chiasm giant glia (xgO), which resides below the lamina, secretes multiple ligands to induce L5 differentiation in response to EGF from photoreceptors. By forcing neuronal differentiation in the lamina, we uncovered that though fated to die, the 'extra' precursor is specified as an L5. Therefore, two precursors are specified as L5s but only one differentiates during normal development. We found that the row of precursors nearest to xgO differentiate into L5s and, in turn, antagonise differentiation signalling to prevent the 'extra' precursors from differentiating, resulting in their death. Thus, an intricate interplay of glial signals and feedback from differentiating neurons defines an invariant and stereotyped pattern of neuronal differentiation and programmed cell death to ensure that lamina columns each contain exactly one L5 neuron
Data availability
All data generated or analysed during this study are included in the manuscript
Article and author information
Author details
Funding
Wellcome Trust (210472/Z/18/Z)
- Vilaiwan M Fernandes
UCL Overseas Research Scholarship
- Anadika R Prasad
UCL Graduate Research Scholarship
- Anadika R Prasad
UCL Biosciences Graduate Research Scholarship
- Matthew P Bostock
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sonia Sen, Tata Institute for Genetics and Society, India
Publication history
- Preprint posted: December 14, 2021 (view preprint)
- Received: February 22, 2022
- Accepted: September 11, 2022
- Accepted Manuscript published: September 12, 2022 (version 1)
- Version of Record published: September 23, 2022 (version 2)
Copyright
© 2022, Prasad et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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