VPS35 deficiency in the embryonic cortex leads to prenatal cell loss and abnormal development of axonal connectivity

Autor: Micaela Roque, Diego Alves Rodrigues de Souza, Martha M. Rangel-Sosa, Mike Altounian, Mélanie Hocine, Jean-Christophe Deloulme, Emmanuel L. Barbier, Fanny Mann, Sophie Chauvet
Přispěvatelé: Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Univ. Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences, GIN, 38000, Grenoble, France, ANR-17-EURE-0029,nEURo*AMU,Marseille NeuroSchool, une formation d'excellence(2017), MANN, Fanny, Marseille NeuroSchool, une formation d'excellence - - nEURo*AMU2017 - ANR-17-EURE-0029 - EURE - VALID
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Molecular and Cellular Neuroscience
Molecular and Cellular Neuroscience, 2022, 120, ⟨10.1016/j.mcn.2022.103726⟩
ISSN: 1044-7431
1095-9327
Popis: International audience; VPS35 is a core component of the retromer complex involved in familial forms of neurodegenerative diseases such as Parkinson's and Alzheimer's disease. In mice, VPS35 is expressed during early brain development. However, previous studies have reported that VPS35 activity is largely dispensable for normal neuronal development and initial elaboration of axonal projections. Here, we evaluated the role of VPS35 in the mouse embryonic brain using two Cre-driver lines that remove Vps35 from the cortex at different prenatal stages. We found that Vps35 mutant mice displayed microcephaly and decreased cortical thickness from the embryonic stages to adulthood. VPS35 also regulates cortical development by affecting a subpopulation of neural progenitor cells and the survival of postmitotic neurons. In addition, we showed that a lack of VPS35 leads to hypoplasia and misrouting of several axonal projections, including the anterior commissure and fornix. Furthermore, VPS35 deficiency impairs the non-autonomous development of thalamocortical axons (TCAs), which show severe disruption of innervation and terminal arborization in the cortex. Together, these data demonstrate that VPS35 plays a greater role in embryonic development of the mammalian brain than it was previously thought.
Databáze: OpenAIRE
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