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Molecular mechanisms involved in the determination of migratory neuroblasts destiny

Grant number: 12/06810-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2012
Effective date (End): October 04, 2017
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal researcher:Marimélia Aparecida Porcionatto
Grantee:Mayara Terra Villela Vieira Mundim
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated scholarship(s):14/00927-0 - Role of galectin-3 in neuroblast migration in a traumatic brain injury model, BE.EP.DR

Abstract

The adult mammal brain presents two well-defined neurogenic areas, the subgranular zone of the hippocampus, which cells integrate the granular zone of the dentate gyrus, and the subventricular zone, designated to produce neuroblasts that migrate through the rostral migratory stream to the olfactory bulb, where they differentiate into interneurons. However, injuries to the central nervous system stimulate neuroblasts to migrate from the neurogenic niche of the subventricular zone, guided by chemoattractives produced at the injured site, while the neuroblast migration to the olfactory bulb still occurs. Although part of the mechanisms and factors involved in the control of neuroblast migration is known, there are some points yet to be clarified. One question refers to the decision made by neuroblast regarding its final destination, the olfactory bulb or an injury. It is still not clear if the neuroblasts that migrate to the injury and the ones that migrate to the olfactory bulb are from the same populations which respond to different chemotactic stimuli, deciding between stimuli depending, for example, of the intensity of the stimulus, or if there are different subpopulations with predetermined destinations. Thus, the aim of our project is to investigate whether there is predetermination of the subventricular zone neuroblasts regarding its destiny, or whether they are susceptible to changes in their migratory route in response to different chemotactic stimuli. To reach this objective, we will use neural stem cell cultured as neurospheres to study the migratory behavior of neuroblasts generated from these cells in response to two soluble chemotactic factors, PK2 and CXCL12. PK2 is produced in the olfactory bulb and is one of the factors responsible for directing neuroblasts to the bulb. The chemokine CXCL12 is one of the main inflammatory cytokines produced in response to injuries and is one of the factors responsible for chemoattraction of neuroblasts to an injury site in the central nervous system. Using the factors and inhibitors of their signaling pathways, we will follow the migration of neuroblasts in vitro using real time microscopy. After knowing the migratory patterns in vitro, we will make an in vivo approach, observing the decision behavior of neuroblasts in a mouse model of traumatic brain injury. We hope that the study of these migratory mechanisms will help to better comprehend neurogenesis in pathological situations and possible application in future therapies. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MUNDIM, MAYARA VIEIRA; ZAMPRONI, LAURA NICOLETI; SARDINHA PINTO, AGNES ARAUJO; GALINDO, LAYLA TESTA; XAVIER, ANDRE MACHADO; GLEZER, ISAIAS; PORCIONATTO, MARIMELIA. A new function for Prokineticin 2: Recruitment of SVZ-derived neuroblasts to the injured cortex in a mouse model of traumatic brain injury. Molecular and Cellular Neuroscience, v. 94, p. 1-10, . (12/06810-1, 12/00652-5)
ZAMPRONI, LAURA N.; MUNDIM, MAYARA T. V. V.; PORCIONATTO, MARIMELIA A.. eurorepair and Regeneration of the Brain: A Decade of Bioscaffolds and Engineered Microtissu. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 09, . (18/12605-8, 13/16533-8, 14/23797-4, 12/06810-1, 14/00927-0)
CHANG, EUN HYUK; ADORJAN, ISTVAN; MUNDIM, MAYARA V.; SUN, BIN; DIZON, MARIA L. V.; SZELE, FRANCIS G.. Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Nichet. FRONTIERS IN NEUROSCIENCE, v. 10, . (12/06810-1, 14/00927-0)

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