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Notch signaling pathway and lateral inhibition in astrocyte dedifferentiation

Grant number: 16/25737-4
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2017
Effective date (End): December 31, 2017
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Marimélia Aparecida Porcionatto
Grantee:Tais Novaki Ribeiro
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

After the central nervous system is injured, astrocytes go through a process of activation, which involves cellular changes to promote tissue repair, leading to the generation of reactive astrocytes. One of the changes is astrocyte dedifferentiation, which can be described as the transition of mature astrocytes to a less differentiated state, similar to neural stem cells. This phenomenon is seen in a subpopulation of reactive astrocytes, and the molecular mechanisms involved in this process are not well known. In this context, the understanding of the process of astrocyte dedifferentiation is necessary for the development of therapeutic strategies that could aim the use of astroglial cells as a source of neural stem cells throughout the CNS. Recent studies suggest that molecular factors involved in neurodevelopment, for example, Wnt, SHH and Notch, are strong candidates to participate in the dedifferentiation process. Lateral inhibition by Notch signaling promotes distinct cellular fates for adjacent cells, which is implicated in numerous processes, such as: in the renew of neural stem cells in the neurogenic niche, in the specification of glial fate, and possibly, in neuronal specification following astrocyte dedifferentiation. Thus, the present study has the following aims: 1) to evaluate basal expression of Notch and Notch ligands by mature astrocytes in vitro; 2) to evaluate the expression and niche marks of Notch and ligands by reactive astrocytes in vitro; and 3) to evaluate the expression of target genes of the Notch signaling pathway by mature and reactive astrocytes in vitro.