Study of cerebellar stem cells and progenitors proliferation stimulated by SHH in mutant mouse for NADPH oxidase 3 (Nox3)

• Grant number: 18/05635-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2018
• End date: December 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Marimélia Aparecida Porcionatto
• Grantee: Sarah Gabrielle Ocanha
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The Nox3eqlb mouse is a mutant line with phenotype of lack of motor coordination and equilibrium selected by a mutagenesis project by ENU (ethylnitroso-urea). This mouse shows increased proliferation of granule cell progenitors (GCPs) during postnatal development (up to 15 days of age), as well as a disorganized Purkinje cell layer. Recently, our group identified the mutation that causes the phenotype as an A> T transversion at position 190 (transcribed sequence) in the Nox3 gene. NOX3 is a member of the NADPH oxidases family, transmembrane proteins that produce reactive oxygen species (ROS). ROS produced by NOX can modulate cell signaling in various physiological processes including proliferation and migration. It is known that during the cerebellum development the Sonic hedgehog (Shh) mitogen plays a fundamental role in the proliferation of neural progenitors. We previously observed that treatment with a NOX inhibitor, apocynin, caused a decrease in the proliferation of GCPs in Nox3eqlb mice, and also altered the expression of Gli1, 2 and 3, transcription factors, and Cyclin D1, target of the Shh pathway. Therefore, our objective is to investigate the participation of NOX and ROS in the Shh signaling pathway in the control of the proliferation of GCPs and cerebellar neural stem cells (CNSC).

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)

MAZZONETTO, P. C.; ARIZA, C. B.; OCANHA, S. G.; DE SOUZ, T. A.; KO, G. M.; MENCK, C. F. M.; MASSIRONI, S. M. G.; PORCIONATTO, M. A.. Mutation in NADPH oxidase 3 (NOX3) impairs SHH signaling and increases cerebellar neural stem/progenitor cell proliferation. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1865, n. 6, p. 1502-1515, JUN 1 2019. (18/05635-8, 14/19204-8, 12/25387-2, 17/18765-4)