Lipophorin receptors regulate mushroom body development and complex behaviors in Drosophila.

BACKGROUND: Drosophila melanogaster lipophorin receptors (LpRs), LpR1 and LpR2, are members of the LDLR family known to mediate lipid uptake in a range of organisms from Drosophila to humans. The vertebrate orthologs of LpRs, ApoER2 and VLDL-R, function as receptors of a glycoprotein involved in development of the central nervous system, Reelin, which is not present in flies. ApoER2 and VLDL-R are associated with the development and function of the hippocampus and cerebral cortex, important association areas in the mammalian brain, as well as with neurodevelopmental and neurodegenerative disorders linked to those regions. It is currently unknown whether LpRs play similar roles in the Drosophila brain. RESULTS: We 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 neurite arborization. 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, suggesting that Drosophila LpRs interact with human Reelin to induce downstream cellular events. CONCLUSIONS: These findings demonstrate that LpRs contribute to MB development and function, supporting the existence of a LpR-dependent signaling in Drosophila, and advance our understanding of the molecular factors functioning in neural systems to generate complex behaviors in this model. Our results further emphasize the importance of Drosophila as a model to investigate the alterations in specific genes contributing to neural disorders.

Balance Between Tooth Size and Tooth Number Is Controlled by Hyaluronan.

While the function of proteins and genes has been widely studied during vertebrate development, relatively little work has addressed the role of carbohydrates. Hyaluronan (HA), also known as hyaluronic acid, is an abundant carbohydrate in embryonic tissues and is the main structural component of the extracellular matrix of epithelial and mesenchymal cells. HA is able to absorb large quantities of water and can signal by binding to cell-surface receptors. During organ development and regeneration, HA has been shown to regulate cell proliferation, cell shape, and migration. Here, we have investigated the function of HA during molar tooth development in mice, in which, similar to humans, new molars sequentially bud off from a pre-existing molar. Using an ex vivo approach, we found that inhibiting HA synthesis in culture leads to a significant increase in proliferation and subsequent size of the developing molar, while the formation of sequential molars was inhibited. By cell shape analysis, we observed that inhibition of HA synthesis caused an elongation and reorientation of the major cell axes, indicating that disruption to cellular orientation and shape may underlie the observed phenotype. Lineage tracing demonstrated the retention of cells in the developing first molar (M1) at the expense of the generation of a second molar (M2). Our results highlight a novel role for HA in controlling proliferation, cell orientation, and migration in the developing tooth, impacting cellular decisions regarding tooth size and number.