Reelin Regulates the Maturation of Dendritic Spines, Synaptogenesis and Glial Ensheathment of Newborn Granule Cells.
The extracellular protein Reelin has an important role in neurological diseases, including epilepsy, Alzheimer's disease and psychiatric diseases, targeting hippocampal circuits. Here we address the role of Reelin in the development of synaptic contacts in adult-generated granule cells (GCs), a neuronal population that is crucial for learning and memory and implicated in neurological and psychiatric diseases. We found that the Reelin pathway controls the shapes, sizes, and types of dendritic spines, the complexity of multisynaptic innervations and the degree of the perisynaptic astroglial ensheathment that controls synaptic homeostasis. These findings show a pivotal role of Reelin in GC synaptogenesis and provide a foundation for structural circuit alterations caused by Reelin deregulation that may occur in neurological and psychiatric disorders.
Developmental Neurobiology and Regeneration Unit, Department of Cell Biology, Parc Científic de Barcelona and Institute of Neurosciences, University of Barcelona, Barcelona 08028, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, Spain.|Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron (VHIR), Barcelona 08023, Spain.
Carles
C
Bosch
Developmental Neurobiology and Regeneration Unit, Department of Cell Biology, Parc Científic de Barcelona and Institute of Neurosciences, University of Barcelona, Barcelona 08028, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, Spain.
Nuria
N
Masachs
Developmental Neurobiology and Regeneration Unit, Department of Cell Biology, Parc Científic de Barcelona and Institute of Neurosciences, University of Barcelona, Barcelona 08028, Spain.
David
D
Exposito-Alonso
Developmental Neurobiology and Regeneration Unit, Department of Cell Biology, Parc Científic de Barcelona and Institute of Neurosciences, University of Barcelona, Barcelona 08028, Spain.
Albert
A
Martínez
Developmental Neurobiology and Regeneration Unit, Department of Cell Biology, Parc Científic de Barcelona and Institute of Neurosciences, University of Barcelona, Barcelona 08028, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, Spain.
Cátia M
CM
Teixeira
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, Spain.|Laboratorio Cajal de Circuitos Corticales, Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Campus de Montegancedo, Madrid 28223, Spain.|Instituto Cajal (Consejo Superior de Investigaciones Científicas), Madrid 28002, Spain.
Isabel
I
Fernaud
Developmental Neurobiology and Regeneration Unit, Department of Cell Biology, Parc Científic de Barcelona and Institute of Neurosciences, University of Barcelona, Barcelona 08028, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, Spain.|Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron (VHIR), Barcelona 08023, Spain.
Lluís
L
Pujadas
Developmental Neurobiology and Regeneration Unit, Department of Cell Biology, Parc Científic de Barcelona and Institute of Neurosciences, University of Barcelona, Barcelona 08028, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, Spain.
Fausto
F
Ulloa
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, Spain.|Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron (VHIR), Barcelona 08023, Spain.|Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain.
Joan X
JX
Comella
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, Spain.|Laboratorio Cajal de Circuitos Corticales, Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Campus de Montegancedo, Madrid 28223, Spain.|Instituto Cajal (Consejo Superior de Investigaciones Científicas), Madrid 28002, Spain.
Javier
J
DeFelipe
Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, Spain.|Laboratorio Cajal de Circuitos Corticales, Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Campus de Montegancedo, Madrid 28223, Spain.|Departamento de Arquitectura y Tecnología de Sistemas Informáticos, Escuela Técnica Superior de Ingenieros Informáticos, Universidad Politécnica de Madrid, Madrid 28660, Spain.
Angel
A
Merchán-Pérez
Developmental Neurobiology and Regeneration Unit, Department of Cell Biology, Parc Científic de Barcelona and Institute of Neurosciences, University of Barcelona, Barcelona 08028, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Madrid 28031, Spain.|Institut de Recerca de l'Hospital Universitari de la Vall d'Hebron (VHIR), Barcelona 08023, Spain.|Institució Catalana de Recerca i Estudis Avançats Academia, Barcelona 08010, Spain.
Eduardo
E
Soriano
D000818:Animals; D001921:Brain / Q000166:cytology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D049229:Dendritic Spines / Q000378:metabolism* / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D021621:Imaging, Three-Dimensional; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D014161:Transduction, Genetic
D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D049452:Green Fluorescent Proteins; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
3D-electron microscopy; FIB/SEM; adult neurogenesis; axospinous synapses; glia