Browsing by Author "Rojo-Cortes, Francisca "

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    Autocrine/Paracrine Slit-Robo Signaling Controls Optic Lobe Development in Drosophila melanogaster
    (2022) Gonzalez-Ramirez, M. Constanza; Rojo-Cortes, Francisca; Candia, Noemi; Garay-Montecinos, Jorge; Guzman-Palma, Pablo; Campusano, Jorge M. M.; Oliva, Carlos
    Cell segregation mechanisms play essential roles during the development of the central nervous system (CNS) to support its organization into distinct compartments. The Slit protein is a secreted signal, classically considered a paracrine repellent for axonal growth through Robo receptors. However, its function in the compartmentalization of CNS is less explored. In this work, we show that Slit and Robo3 are expressed in the same neuronal population of the Drosophila optic lobe, where they are required for the correct compartmentalization of optic lobe neuropils by the action of an autocrine/paracrine mechanism. We characterize the endocytic route followed by the Slit/Robo3 complex and detected genetic interactions with genes involved in endocytosis and actin dynamics. Thus, we report that the Slit-Robo3 pathway regulates the morphogenesis of the optic lobe through an atypical autocrine/paracrine mechanism in addition to its role in axon guidance, and in association with proteins of the endocytic pathway and small GTPases.
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    Lamp1 Deficiency Enhances Sensitivity to α-Synuclein and Oxidative Stress in Drosophila Models of Parkinson Disease
    (2022) Rahmani, Zohra; Surabhi, Satya; Rojo-Cortes, Francisca; Dulac, Amina; Jenny, Andreas; Birman, Serge
    Parkinson disease (PD) is a common neurodegenerative condition affecting people predominantly at old age that is characterized by a progressive loss of midbrain dopaminergic neurons and by the accumulation of alpha-synuclein-containing intraneuronal inclusions known as Lewy bodies. Defects in cellular degradation processes such as the autophagy-lysosomal pathway are suspected to be involved in PD progression. The mammalian Lysosomal-associated membrane proteins LAMP1 and LAMP2 are transmembrane glycoproteins localized in lysosomes and late endosomes that are involved in autophagosome/lysosome maturation and function. Here, we show that the lack of Drosophila Lamp1, the homolog of LAMP1 and LAMP2, severely increased fly susceptibility to paraquat, a pro-oxidant compound known as a potential PD inducer in humans. Moreover, the loss of Lamp1 also exacerbated the progressive locomotor defects induced by the expression of PD-associated mutant alpha-synuclein A30P (alpha-synA30P) in dopaminergic neurons. Remarkably, the ubiquitous re-expression of Lamp1 in a mutant context fully suppressed all these defects and conferred significant resistance towards both PD factors above that of wild-type flies. Immunostaining analysis showed that the brain levels of alpha-synA30P were unexpectedly decreased in young adult Lamp1-deficient flies expressing this protein in comparison to non-mutant controls. This suggests that Lamp1 could neutralize alpha-synuclein toxicity by promoting the formation of non-pathogenic aggregates in neurons. Overall, our findings reveal a novel role for Drosophila Lamp1 in protecting against oxidative stress and alpha-synuclein neurotoxicity in PD models, thus furthering our understanding of the function of its mammalian homologs.
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    Lipophorin receptors regulate mushroom bodies development and participate in learning, memory, and sleep in flies
    (2021) Rojo-Cortes, Francisca ; Tapia-Valladares, Victoria ; Fuenzalida-Uribe, Nicolas ; Hidalgo, Sergio ; Roa, Candy B. ; Gonzalez-Ramirez, Maria-Constanza ; Oliva, Carlos ; Campusano, Jorge M. ; Marzolo, Maria-Paz