Punal, V. M. | bioRxiv Science

bioRxiv2026

Modular presynaptic assemblages scale to postsynaptic partner number

Behavioral diversification can arise through, and is constrained by, evolutionary and inter-individual differences in neural circuit development. Moreover, alteration of focal neural parameters changes the environment in which cells connect into circuits. In the mushroom body, an associative learning center of arthropods, the number of principal Kenyon cells varies widely across species and among individuals. How such variation is developmentally accommodated by projection neurons, which provide sensory input to Kenyon cells, is not understood. In Drosophila melanogaster, we previously demonstrated that projection neurons scale their presynaptic bouton number to Kenyon cell population size. Here, we identify the developmental mechanisms underlying this input flexibility. Boutons arise from projection neuron axonal collaterals; we find that a PNs collateral number is subtype-specific and serves as the substrate through which bouton number scales to Kenyon cell population size. Independent of projection neuron identity or Kenyon cell number, individual collaterals most often produce just one bouton, suggesting collaterals are modular cell biological bouton units. Developing projection neurons initially overproduce nascent collaterals in the early pupa. The set of nascent collaterals that mature and eventually bear boutons is conditional on Kenyon cell number, thereby executing scaling. Finally, early boutons bear filopodia that frequently contact neighboring PN processes, suggesting that bouton-bouton interactions contribute to shaping these structures.

neuroscience↗

bioRxiv2019

Large-scale death of retinal astrocytes duringnormal development mediated by microglia

Naturally-occurring cell death is a fundamental developmental mechanism for regulating cell numbers and sculpting developing organs. This is particularly true in the central nervous system, where large numbers of neurons and oligodendrocytes are eliminated via apoptosis during normal development. Given the profound impact of death upon these two major cell populations, it is surprising that developmental death of another major cell type - the astrocyte - has rarely been studied. It is presently unclear whether astrocytes are subject to significant amounts of developmental death, or how it occurs. Here we address these questions using mouse retinal astrocytes as our model system. We show that the total number of retinal astrocytes declines by over 3-fold during a death period spanning postnatal days 5-14. Surprisingly, these astrocytes do not die by apoptosis, the canonical mechanism underlying the vast majority of developmental cell death. Instead, we find that microglia kill and engulf astrocytes to mediate their developmental removal. Genetic ablation of microglia inhibits astrocyte death, leading to a larger astrocyte population size at the end of the death period. However, astrocyte death is not completely blocked in the absence of microglia, apparently due to the ability of astrocytes to engulf each other. Nevertheless, mice lacking microglia showed significant anatomical changes to the retinal astrocyte network, with functional consequences for the astrocyte-associated vasculature leading to retinal hemorrhage. These results establish a novel modality for naturally-occurring cell death, and demonstrate its importance for formation and integrity of the retinal gliovascular network.

neuroscience↗