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SCRATCH2 in embryonic and stem cell neural differentiation.

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Author(s):
Tatiane Yumi Nakamura Kanno
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Chao Yun Irene Yan; Federico David Brown Almeida; Nathalie Cella; Júlia Pinheiro Chagas da Cunha; José Xavier Neto
Advisor: Chao Yun Irene Yan
Abstract

SCRATCH2 is a transcription factor involved in neural development expressed in postmitotic neural cells. Here, we identify that the nuclear retention of SCRATCH2 is controlled by the zinc-finger domain. The repressor activity is modulated by the SCRATCH domain and is independent of the SNAG domain. An analysis of SCRATCH2 through homology comparison identified a N-terminal conserved sequence containing two phosphorylatable residues, Y77 and S78. Single mutation in Y77 or S78 reduces SCRATCH2 repression ability while concomitant mutation in both rescue SCRATCH2 function. Our data suggest that the zinc-finger domain is responsible for nuclear retention of SCRATCH2 while residues Y77 and S78 are relevant for the protein correct conformation. In mouse embryonic stem cells neural induced towards corticogenesis, SCRATCH2 KO increases the levels of intermediate progenitors (IP) markers and reduces the level of early born neurons markers. This data suggests that SCRATCH2 plays a role in the maintenance of IP pool, thereby regulating the onset of neural differentiation. (AU)

FAPESP's process: 11/20253-5 - Neurogenic function of cScratch2 transcription factor in dorsal root ganglia and in the differentiation of embryonic stem cells.
Grantee:Tatiane Yumi Nakamura Kanno
Support Opportunities: Scholarships in Brazil - Doctorate