Biology subjects

Rojo-Cortes, F.

Publications and source records attributed to Rojo-Cortes, F..

4 recordsLinked to original sources

bioRxiv2026

Weckle is a molecular switch that diverts Toll signalling from innate immunity towards growth by engaging Yki

The mechanisms underlying how the brain can switch from a plastic to a degenerative state are unknown. Tolls and Toll-Like receptors (TLRs) could be involved since they underlie both neuroinflammation and structural brain plasticity. Here, we show that the Toll signalling adaptor Weckle (Wek) - a ZAD-Zinc-finger transcription factor - can switch the response from promoting innate immunity or cell death, to inducing growth instead. Myristoylated Wek binds Tolls at the membrane, and concerted PI3K and Toll signalling drive its nuclear translocation. Wek interacts with Yorkie (Yki) - the key regulator of growth restrained by Hippo - enabling its nuclear shuttling. Remarkably, Wek blocks innate immunity. Instead, Wek and Yki together drive glial cell proliferation and growth. Through this mechanism, Toll signalling could promote structural brain plasticity via Wek and Yki downstream. As Tolls and Yki are widespread, these findings could have important implications for understanding also regeneration and cancer.

developmental biology↗

bioRxiv2025

The neurotrophin DNT-2 regulates cell survival and connectivity via the Toll-2 receptor during visual system development of Drosophila

During development, neurons are produced in excess and those that receive trophic support are maintained, whereas excess neurons are eliminated, enabling the establishment of appropriate neural circuits. In vertebrates, neurotrophin ligands promote cell survival during periods of naturally occurring cell death, by signalling through p75 and Trk receptors. In the Drosophila optic lobe, a wave of apoptosis occurs during neural circuit development; however, whether this also involves neurotrophism remains unresolved. Drosophila neurotrophins (DNTs) are encoded by spatzle (spz) paralogue genes and bind Toll receptors instead. Here, we focused on DNT-3 (previously known as spz-3) and DNT-2 (also known as spz-5) to ask whether they underlie neurotrophism in visual system development. We show that DNT-3 (spz-3) and DNT-2 (spz-5) are both expressed in the retina and in medulla neurons, and multiple Tolls are expressed across lamina and medulla neurons. Over-expression of DNT-3 (spz-3) and DNT-2 (spz-5) could rescue natural occurring cell death, whereas their loss of function caused cell death, showing that DNT-3 and DNT-2 can, and are required to, promote cell survival during optic lobe development. Importantly, DNT-2 is expressed in Mi1 neurons and Toll-2 in connecting L1 neurons. We show that DNT-2 functions in concert with Toll-2, as Toll-2 RNAi knock-down prevented the rescue of apoptosis by DNT-2 over-expression and all Toll-2+ neurons were lost in DNT-2 mutants. Furthermore, alterations in DNT-2 or Toll-2 expression levels impaired connectivity of L1 neurons at the M1 medulla layer and altered dendritic morphology of L1 neurons. These data suggest that L1 neurons could take up DNT-2 secreted from medulla neurons during the establishment of connectivity patterns. As DNT-3 (spz-3) and DNT-2 (spz-5) are expressed in the medulla and they could influence both lamina and medulla neurons, this suggests that their function maintaining cell survival could enable the stabilisation or alignment of connected neurons across medulla columns.

developmental biology↗

bioRxiv2024

Drospondin, a novel glial-secreted glycoprotein, controls the development and function of the Drosophila nervous system

Reelin is a secreted glycoprotein with roles in the development of the mammalian neocortex, hippocampus and cerebellum. This vertebrate signaling molecule also contributes to adult brain function. Mammalian Reelin increases the complexity of Drosophila Mushroom Body (MB) neurites, an effect mediated by LpR1 and LpR2, the orthologs of mammalian Reelin receptors. Paradoxically, to date, no Reelin ortholog has been described in Drosophila. Here, we report that the protein product of the uncharacterized Drosophila CG17739 gene, which we named Drospondin, shares sequence homology with vertebrate F-spondin and Reelin. We show that Drospondin is expressed in glial cells and is crucial for MB development. Our results also show that Drospondin genetically interacts with LpRs and that human Reelin rescues structural defects in Drospondin-deficient flies. Furthermore, Drospondin-deficient flies exhibit altered sleep homeostasis, locomotion, and social behaviors. Our results reveal that flies express a functional homolog of mammalian Reelin that controls the development and function of the Drosophila nervous system.

developmental biology↗

bioRxiv2021

Lipophorin receptors regulate mushroom bodies development and participate in learning, memory, and sleep in flies

BackgroundDrosophila melanogaster Lipophorin Receptors (LpRs), LpR1 and LpR2, mediate lipid uptake. The orthologs of these receptors in vertebrates, ApoER2 and VLDL-R, bind Reelin, a glycoprotein not present in flies. These receptors are associated with the development and function of the hippocampus and cerebral cortex, important association areas in the mammalian brain. It is currently unknown whether LpRs play similar roles in the Drosophila brain. ResultsWe report that LpR-deficient flies exhibit impaired olfactory memory and sleep patterns, which seem to reflect anatomical defects found in a critical brain association area, the Mushroom Bodies (MB). Moreover, cultured MB neurons respond to mammalian Reelin by increasing the complexity of their neurites. This effect depends on LpRs and Dab, the Drosophila ortholog of the reelin signaling adaptor protein Dab1. In vitro, two of the long isoforms of LpRs allow the internalization of Reelin. ConclusionsThese findings demonstrate that LpRs contribute to MB development and function, supporting the existence of LpR-dependent signaling in Drosophila.

neuroscience↗