Role of Wnt/beta-catenin signalling in astrocyte dedifferentiation

• Grant number: 15/08151-3
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2015
• End date: March 31, 2017
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Marimélia Aparecida Porcionatto
• Grantee: Agnes Araujo Sardinha Pinto
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Neurogenesis in adult mammalian brain occurs continuously in two restricted and specialized areas, the subgranular zone of hippocampus and the subventricular zone. Besides neurogenesis in physiologic conditions, new neural cells are also produced in response to cerebral injuries, such as ischemia and trauma. Astrocytes play an important role in response to lesions in the central nervous system (CNS), taking part in determination of cellular fate and proliferative control at neurogenic regions. Another astrocyte response is the transition of a subpopulation into an undifferentiated state. This process is characterized by phenotypic changes and entrance in a proliferative state, suggesting the occurrence of cellular dedifferentiation, i.e. astrocytes begin to behave as neural stem cells. Astrocyte reaction is well recognized in several injury types, however, it is not completely understood to what extent reactive astrocytes play a role in the constitution of glial scar as well as their effects on other CNS cells. Recent studies suggest a possible role of Wnt/beta-catenin signalling in astrocyte dedifferetiation process, which is the hypothesis and focus of this project. The acquisition of stem cell properties by astrocytes through dedifferentiation may contribute to generate new neural cells at a lesion site, overcoming issues related to recruitment and migration of neural progenitors from the subventricular zone. Therefore, understanding the molecular mechanisms and factors involved in astrocyte dedifferentiation is crucial to allow the identification of therapeutic targets that may optimize the generation of new multipotent cells, promoting better cerebral regeneration and recovery after a brain lesion.