Glial-secreted Netrins regulate Robo1/Rac1-Cdc42 signaling threshold levels during Drosophila asymmetric neural stem/progenitor cell division. 2022

Ana de Torres-Jurado, and Sandra Manzanero-Ortiz, and Ana Carmena
Developmental Neurobiology Department, Instituto de Neurociencias, Consejo Superior de Investigaciones Científicas, Universidad Miguel Hernández, Avda. Ramón y Cajal s/n, Sant Joan d'Alacant, 03550 Alicante, Spain.

Asymmetric stem cell division (ASCD) is a key mechanism in development, cancer, and stem cell biology. Drosophila neural stem cells, called neuroblasts (NBs), divide asymmetrically through intrinsic mechanisms. Here, we show that the extrinsic axon guidance cues Netrins, secreted by a glial niche surrounding larval brain neural stem cell lineages, regulate NB ASCD. Netrin-Frazzled/DCC signaling modulates, through Abelson kinase, Robo1 signaling threshold levels in Drosophila larval brain neural stem and progenitor cells of NBII lineages. Unbalanced Robo1 signaling levels induce ectopic NBs and progenitor cells due to failures in the ASCD process. Mechanistically, Robo1 signaling directly impinges on the intrinsic ASCD machinery, such as aPKC, Canoe/Afadin, and Numb, through the small GTPases Rac1 and Cdc42, which are required for the localization in mitotic NBs of Par-6, a Cdc42 physical partner and a core component of the Par (Par-6-aPKC-Par3/Bazooka) apical complex.

UI MeSH Term Description Entries
D007605 Juvenile Hormones Compounds, either natural or synthetic, which block development of the growing insect. Insect Growth Regulator,Insect Growth Regulators,Juvenile Hormone,Growth Regulators, Insect,Regulators, Insect Growth,Growth Regulator, Insect,Hormone, Juvenile,Hormones, Juvenile,Regulator, Insect Growth
D007814 Larva Wormlike or grublike stage, following the egg in the life cycle of insects, worms, and other metamorphosing animals. Maggots,Tadpoles,Larvae,Maggot,Tadpole
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D011971 Receptors, Immunologic Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere. Immunologic Receptors,Immunologic Receptor,Immunological Receptors,Receptor, Immunologic,Receptors, Immunological
D004330 Drosophila A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology. Fruit Fly, Drosophila,Drosophila Fruit Flies,Drosophila Fruit Fly,Drosophilas,Flies, Drosophila Fruit,Fly, Drosophila Fruit,Fruit Flies, Drosophila
D004331 Drosophila melanogaster A species of fruit fly frequently used in genetics because of the large size of its chromosomes. D. melanogaster,Drosophila melanogasters,melanogaster, Drosophila
D000075385 Netrins A family of extracellular proteins that are related structurally to LAMININ. They function as CHEMOTACTIC FACTORS for CELL MIGRATION and AXON GUIDANCE, acting as chemoattractants for some cell types, and as chemorepellents for others. Netrin,Netrin Family
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D058953 Neural Stem Cells Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA. Cell, Neural Stem,Cells, Neural Stem,Neural Stem Cell,Stem Cell, Neural,Stem Cells, Neural
D060049 Asymmetric Cell Division Unequal cell division that results in daughter cells of different sizes. Asymmetric Stem Cell Division,Asymmetric Stem Cell Differentiation,Asymmetric Cell Divisions,Cell Division, Asymmetric,Cell Divisions, Asymmetric,Division, Asymmetric Cell,Divisions, Asymmetric Cell

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