scholarly journals OTX2 signals from the choroid plexus to regulate adult neurogenesis

2018 ◽  
Author(s):  
Anabelle Planques ◽  
Vanessa Oliveira Moreira ◽  
Chantal Dubreuil ◽  
Alain Prochiantz ◽  
Ariel A Di Nardo
Keyword(s):  
Extracellular Matrix ◽  
Cerebrospinal Fluid ◽  
Olfactory Bulb ◽  
Choroid Plexus ◽  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Supporting Cells ◽  
Multi Level ◽  
Newborn Neurons ◽  
Migratory Stream

AbstractProliferation and migration during adult neurogenesis are regulated by a microenvironment of signaling molecules originating from local vasculature, from cerebrospinal fluid produced by the choroid plexus, and from local supporting cells including astrocytes. Here, we focus on the function of OTX2 homeoprotein transcription factor in the mouse adult ventricular-subventricular zone (V-SVZ) which generates olfactory bulb neurons. We find that OTX2 secreted by choroid plexus is transferred to supporting cells of the V-SVZ and rostral migratory stream. Deletion of Otx2 in choroid plexus affects neuroblast migration and reduces the number of olfactory bulb newborn neurons. Adult neurogenesis was also decreased by expressing secreted single-chain antibodies to sequester OTX2 in the cerebrospinal fluid, demonstrating the importance of non-cell autonomous OTX2. We show that OTX2 activity modifies extracellular matrix components and signaling molecules produced by supporting astrocytes. Thus, we reveal a multi-level and non-cell autonomous role of a homeoprotein and reinforce the choroid plexus and astrocytes as key niche compartments affecting adult neurogenesis.Significance StatementCerebrospinal fluid, local vasculature and non-neurogenic astrocytes are niche compartments that provide a microenvironment for regulating adult mouse neurogenesis. We show that OTX2 homeoprotein secreted by choroid plexus into the cerebrospinal fluid is transferred into non-neurogenic astrocytes of the ventricular-subventricular zone and rostral migratory stream where it regulates extracellular matrix and signaling factors. This non-cell-autonomous activity impacts the number of newborn neurons that integrate the olfactory bulb. Thus, we reveal a multi-level role for OTX2 and reinforce the choroid plexus as a key niche compartment affecting adult neurogenesis.

scholarly journals Effects of Brain Size on Adult Neurogenesis in Shrews

2021 ◽  
Vol 22 (14) ◽  
pp. 7664
Author(s):  
Katarzyna Bartkowska ◽  
Krzysztof Turlejski ◽  
Beata Tepper ◽  
Leszek Rychlik ◽  
Peter Vogel ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Molecular Mechanisms ◽  
Brain Size ◽  
Hippocampal Formation ◽  
Small Animals ◽  
Suncus Murinus ◽  
The Brain ◽  
Neomys Fodiens ◽  
Migratory Stream

Shrews are small animals found in many different habitats. Like other mammals, adult neurogenesis occurs in the subventricular zone of the lateral ventricle (SVZ) and the dentate gyrus (DG) of the hippocampal formation. We asked whether the number of new generated cells in shrews depends on their brain size. We examined Crocidura russula and Neomys fodiens, weighing 10–22 g, and Crocidura olivieri and Suncus murinus that weigh three times more. We found that the density of proliferated cells in the SVZ was approximately at the same level in all species. These cells migrated from the SVZ through the rostral migratory stream to the olfactory bulb (OB). In this pathway, a low level of neurogenesis occurred in C. olivieri compared to three other species of shrews. In the DG, the rate of adult neurogenesis was regulated differently. Specifically, the lowest density of newly generated neurons was observed in C. russula, which had a substantial number of new neurons in the OB compared with C. olivieri. We suggest that the number of newly generated neurons in an adult shrew’s brain is independent of the brain size, and molecular mechanisms of neurogenesis appeared to be different in two neurogenic structures.

scholarly journals OTX2 homeoprotein functions in adult choroid plexus

2021 ◽  
Author(s):  
Anabelle Planques ◽  
Vanessa Oliveira Moreira ◽  
David Benacom ◽  
Clémence Bernard ◽  
Laurent Jourdren ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Choroid Plexus ◽  
Stress Responses ◽  
Subventricular Zone ◽  
Adult Mouse ◽  
Mass Spectrometry Analysis ◽  
Mrna Isoforms ◽  
Spectrometry Analysis ◽  
Protein Partners ◽  
Brain Homeostasis

AbstractChoroid plexus secretes cerebrospinal fluid important for brain development and homeostasis. The OTX2 homeoprotein is critical for choroid plexus development and remains highly expressed in adult choroid plexus. Through RNA sequencing analyses of constitutive and conditional knockdown adult mouse models, we reveal putative roles for OTX2 in choroid plexus function, including cell signaling and adhesion, and show that it regulates the expression of factors secreted into cerebrospinal fluid, notably transthyretin. We show that Otx2 expression impacts choroid plexus immune and stress responses, and also affects splicing which leads to changes in mRNA isoforms of proteins implicated in oxidative stress response and DNA repair. Through mass spectrometry analysis of OTX2 protein partners in the choroid plexus, and in known non-cell autonomous target regions such as visual cortex and ventricular-subventricular zone, we identified putative targets involved in cell adhesion, chromatin structure and RNA processing. Thus, OTX2 retains important roles in choroid plexus function and brain homeostasis throughout life.

scholarly journals Targeting Adult Neurogenesis for Poststroke Therapy

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jianfei Lu ◽  
Anatol Manaenko ◽  
Qin Hu
Keyword(s):  
Stem Cells ◽  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Tissue Repair ◽  
Therapeutic Interventions ◽  
Subgranular Zone ◽  
Brain Repair ◽  
Function Recovery ◽  
Newborn Neurons ◽  
And Function

Adult neurogenesis mainly occurs at the subventricular zone (SVZ) on the walls of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus (DG). However, the majority of newborn neurons undergo programmed cell death (PCD) during the period of proliferation, migration, and integration. Stroke activates neural stem cells (NSCs) in both SVZ and SGZ. This process is regulated by a wide variety of signaling pathways. However, the newborn neurons derived from adult neurogenesis are insufficient for tissue repair and function recovery. Thus, enhancing the endogenous neurogenesis driven by ischemia and promoting the survival of newborn neurons can be promising therapeutic interventions for stroke. Here, we present an overview of the process of adult neurogenesis and the potential of stroke-induced neurogenesis on brain repair.

scholarly journals Erratum to: Anosmin-1 over-expression increases adult neurogenesis in the subventricular zone and neuroblast migration to the olfactory bulb

2016 ◽  
Vol 221 (9) ◽  
pp. 4741-4741
Author(s):  
Diego García-González ◽  
Verónica Murcia-Belmonte ◽  
Pedro F. Esteban ◽  
Felipe Ortega ◽  
David Díaz ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Over Expression ◽  
Neuroblast Migration

scholarly journals Fractone bulbs derive from ependymal cells and their laminin composition influence the stem cell niche in the subventricular zone

2016 ◽  
Author(s):  
Marcos Assis Nascimento ◽  
Lydia Sorokin ◽  
Tatiana Coelho-Sampaio
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Stem Cell Niche ◽  
Ependymal Cells ◽  
Cell Niche

AbstractFractones are extracellular matrix structures in the neural stem cell niche of the subventricular zone (SVZ), where they appear as round deposits named bulbs or thin branching lines called stems. Their cellular origin and what determines their localization at this site is poorly studied and it remains unclear whether they influence neural stem and progenitor cells formation, proliferation and/or maintenance. To address these questions, we analyzed whole mount preparations of the lateral ventricle by confocal microscopy using different extracellular matrix and cell markers. We found that bulbs are rarely connected to stems and that they contain laminin α5 and α2 chains, respectively. Fractone bulbs were profusely distributed throughout the SVZ and appeared associated with the center of pinwheels, a critical site for adult neurogenesis. We demonstrate that bulbs appear at the apical membrane of ependymal cells at the end of the first week after birth. The use of transgenic mice lacking laminin α5 gene expression (Lama5) in endothelium and in FoxJ1-expressing ependymal cells, revealed ependymal cells as the source of laminin α5-containing fractone bulbs. Loss of laminin α5 from bulbs correlated with a 60% increase in cell proliferation, as determined by PH3 staining, and with a selective reduction in the number of quiescent neural stem cells in the SVZ. These results indicate that fractones are a key component of the SVZ and suggest that laminin α5 modulates the physiology of the neural stem cell niche.Significance StatementOur work unveils key aspects of fractones, extracellular matrix structures present in the SVZ that still lack a comprehensive characterization. We show that fractones extensively interact with neural stem cells, whereas some of them are located precisely at pinwheel centers, which are hotspots for adult neurogenesis. Our results also demonstrate that fractones increase in size during aging and that their interactions with NSPCs become more complex in old mice. Lastly, we show that fractone bulbs are produced by ependymal cells and that their laminin content regulates neural stem cells.

Anosmin-1 over-expression increases adult neurogenesis in the subventricular zone and neuroblast migration to the olfactory bulb

2014 ◽  
Vol 221 (1) ◽  
pp. 239-260 ◽  
Author(s):  
Diego García-González ◽  
Verónica Murcia-Belmonte ◽  
Pedro F. Esteban ◽  
Felipe Ortega ◽  
David Díaz ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Over Expression ◽  
Neuroblast Migration
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