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Analysis of the RECK tumor suppressor gene's role in asymmetric cell division

Grant number: 16/18277-7
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): January 10, 2017
Effective date (End): January 05, 2018
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Mari Cleide Sogayar
Grantee:Marina Trombetta Lima
Supervisor abroad: Makoto Noda
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Local de pesquisa : Kyoto University, Japan  
Associated to the scholarship:15/26328-8 - Comparative analysis of the RECK tumor suppressor gene role in glioblastoma stem cell sub-population and in normal neural stem cells, BP.PD


Asymmetric cell divisions of progenitor cells are modulated by the Notch signaling pathway and render daughter cells with different differentiation potentials. The tumor suppressor gene Reck was first described by Professor Noda's group in 1998 and codes an 110KDa protein with MMP inhibitory function. Reck regulates the ectodomain shedding of Notch ligands and Reck deficient neural precursor cells undergo precocious differentiation linked to impaired Notch signaling during cortical development. Additionally, Reck downregulation in mesenchymal stem cells favors the adipogenic differentiation pathway. Taken together these results suggest that Reck directly influence stem cell fate determination. In the present project, we propose to investigate the role of Reck transcripts in stem cells fate determination through the analysis of their influence in asymmetric cell division. We propose to investigate the consequences of Reck depletion on the architecture formation of two different tissues in which asymmetric cell division is crucial: skin and retina. A comparative analysis of wild type versus ReckCreER mice skin and retina explants, from different developmental stages, will be performed to evaluate the asymmetric versus symmetric divisions rate and precursors cells fate. In addition, mice stem cells form the same animals will be seeded upon symmetric or asymmetric adhesion surface micro-patterning and submitted to neurodifferentiation protocols to better characterize Reck´s role in mediating external microenvironment signals favoring asymmetric or asymmetric divisions. We hope that the present study will contribute to the overall understanding of symmetric/asymmetric cell division switch regulation and may lead to advances in the comprehension of the origin of different pathologies such as cancer.

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)
ASSIS-RIBAS, THAIS; FORNI, MARIA FERNANDA; BROCHADO WINNISCHOFER, SHEILA MARIA; SOGAYAR, MARI CLEIDE; TROMBETTA-LIMA, MARINA. Extracellular matrix dynamics during mesenchymal stem cells differentiation. Developmental Biology, v. 437, n. 2, p. 63-74, MAY 15 2018. Web of Science Citations: 7.

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