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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2016.tde-10112016-090637
Document
Author
Full name
Tatiane Yumi Nakamura Kanno
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Yan, Chao Yun Irene (President)
Almeida, Federico David Brown
Cella, Nathalie
Cunha, Júlia Pinheiro Chagas da
Xavier Neto, José
Title in Portuguese
SCRATCH2 na diferenciação neural em embriões e em células-tronco.
Keywords in Portuguese
Células-tronco embrionárias
Corticogênese
Embrião de galinha
Fator de transcrição
Neurogênese
SCRATCH2
Abstract in Portuguese
SCRATCH2 é um fator de transcrição envolvido no desenvolvimento neural expresso em células pós-mitóticas. Identificamos que a retenção nuclear de SCRATCH2 é dada pelo domínio zinc-finger. A atividade repressora é modulada pelo domínio SCRATCH e não depende do domínio SNAG. O alinhamento de ortólogos de SCRATCH2 identificou uma sequência conservada na região N-terminal contendo os resíduos de fosforiláveis Y77 e S78. Mutação em Y77 ou S78 reduz a capacidade repressora de SCRATCH2, enquanto mutações em ambos resíduos resgatam sua função. Nossos dados sugerem que o domínio zinc-finger é responsável pela localização nuclear enquanto a atividade repressora é mediada pelo domínio SCRATCH. Já a identidade de Y77 e S78 é importante para a conformação correta proteína. O nocaute de SCRATCH2 aumenta a expressão de marcadores de progenitores intermediários (IP) e reduz o a expressão de marcadores de neurônios pós-mitóticos durante a neurodiferenciação de células-tronco. Esses dados sugerem que SCRATCH2 atua na manutenção de IP, e participa do início da diferenciação neural.
Title in English
SCRATCH2 in embryonic and stem cell neural differentiation.
Keywords in English
Chicken embryo
Corticogenesis
Embryonic stem-cells
Neurogenesis
SCRATCH2
Transcription factor
Abstract in English
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.
 
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Release Date
2020-11-10
Publishing Date
2016-11-10
 
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