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Dentate Gyrus Development Requires ERK Activity to Maintain Progenitor Population and MAPK Pathway Feedback Regulation.
Vithayathil, Joseph; Pucilowska, Joanna; Goodnough, L Henry; Atit, Radhika P; Landreth, Gary E.
Afiliação
  • Vithayathil J; Departments of Neurosciences.
  • Pucilowska J; Departments of Neurosciences.
  • Goodnough LH; Pathology, and.
  • Atit RP; Biology, Case Western Reserve University, Cleveland, Ohio 44106.
  • Landreth GE; Departments of Neurosciences, gel2@case.edu.
J Neurosci ; 35(17): 6836-48, 2015 Apr 29.
Article em En | MEDLINE | ID: mdl-25926459
ABSTRACT
The ERK/MAPK pathway is an important developmental signaling pathway. Mutations in upstream elements of this pathway result in neuro-cardio-facial cutaneous (NCFC) syndromes, which are typified by impaired neurocognitive abilities that are reliant upon hippocampal function. The role of ERK signaling during hippocampal development has not been examined and may provide critical insight into the cause of hippocampal dysfunction in NCFC syndromes. In this study, we have generated ERK1 and conditional ERK2 compound knock-out mice to determine the role of ERK signaling during development of the hippocampal dentate gyrus. We found that loss of both ERK1 and ERK2 resulted in 60% fewer granule cells and near complete absence of neural progenitor pools in the postnatal dentate gyrus. Loss of ERK1/2 impaired maintenance of neural progenitors as they migrate from the dentate ventricular zone to the dentate gyrus proper, resulting in premature depletion of neural progenitor cells beginning at E16.5, which prevented generation of granule cells later in development. Finally, loss of ERK2 alone does not impair development of the dentate gyrus as animals expressing only ERK1 developed a normal hippocampus. These findings establish that ERK signaling regulates maintenance of progenitor cells required for development of the dentate gyrus.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco / Regulação da Expressão Gênica no Desenvolvimento / Giro Denteado / Proteína Quinase 1 Ativada por Mitógeno / Sistema de Sinalização das MAP Quinases / Retroalimentação Fisiológica Limite: Animals Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco / Regulação da Expressão Gênica no Desenvolvimento / Giro Denteado / Proteína Quinase 1 Ativada por Mitógeno / Sistema de Sinalização das MAP Quinases / Retroalimentação Fisiológica Limite: Animals Idioma: En Ano de publicação: 2015 Tipo de documento: Article