Universidade de Lisboa Repositório da Universidade de Lisboa

Repositório da Universidade de Lisboa >
Faculdade de Ciências (FC) >
FC - Teses de Doutoramento >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10451/1604

Título: Rere (Atrophin2) in the left-right coordination of somitogenesis
Autor: Neto, Gonçalo Cadete Vilhais, 1978-
Orientador: Henrique, Domingos, 1960-
Thorsteinsdóttir, Sólveig, 1962-
Palavras-chave: Vertebrados
Somitogénese
Ácido retinóico
Rere
Miogénese
Espectrometria de massa
Biologia do desenvolvimento
Teses de doutoramento
Issue Date: 2009
Resumo: One of the most striking features of the vertebrate body plan organization is its bilateral symmetry, most evident at the level of the vertebrae and skeletal muscles. During my PhD, I showed that Rere (Atrophin2)-deficient mouse embryos form asymmetrical somites in a temporally defined window. During the time period spanning the formation of somites 7 to 13 in Rere mutants, there is a lack of left-right coordination of the oscillatory behavior of the cyclic genes and of determination front regression. This results in the desynchronization of the segmentation cascade, leading to a delay of the clock oscillations and wavefront regression on the right side, in turn, resulting in a delay of somite formation from the right rostral PSM. The somite laterality defect in the mutant is controlled by the left-right signaling machinery. Rere mutants are similar to embryos deprived of retinoic acid (RA). I then showed that Rere controls RA signaling, which is required to maintain somite symmetry by buffering Fgf8 action in the left-right signaling pathway. Rere is recruited to the promoter of RA targets (e.g., RAR-beta) but does not bind to the RAR-RXR complex. Rere binds to the nuclear receptor NR2F2 (COUP-TF2), which is also recruited to the RAR-beta promoter. Asymmetrical expression of NR2F2 in the PSM overlaps with the asymmetry of the RA signaling response, supporting a role for NR2F2 in the control of somite symmetry downstream of Rere and RA. Rere is also implicated in other RA-dependent processes, like myogenesis, supporting a more widespread function of Rere in RA signaling. By mass spectrometry, we identified Rereassociated proteins that will lead us to better comprehend RA signaling and the left-right coordination of somitogenesis. In humans, major defects of the bilateral symmetry of somite derivatives are observed at the spine level in a class of diseases called scoliosis. A better understanding of the Rere dependent, RA pathway described in this work, which affects the symmetry of vertebral precursors, could be clinically relevant to human spine pathologies.
Resumo alargado em portuguê disponível no documento
Descrição: Tese de doutoramento, Biologia (Biologia do Desenvolvimento), 2009, Universidade de Lisboa, Faculdade de Ciências
URI: http://sibul.reitoria.ul.pt/F/?func=item-global&doc_library=ULB01&type=03&doc_number=000555038
http://hdl.handle.net/10451/1604
Appears in Collections:FC - Teses de Doutoramento

Files in This Item:

File Description SizeFormat
17775_ulsd_re321_Tese_Goncalo_Neto.pdf12,27 MBAdobe PDFView/Open
Restrict Access. You can request a copy!
Statistics
FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpaceOrkut
Formato BibTex mendeley Endnote Logotipo do DeGóis 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

  © Universidade de Lisboa / SIBUL
Alameda da Universidade | Cidade Universitária | 1649-004 Lisboa | Portugal
Tel. +351 217967624 | Fax +351 217933624 | repositorio@reitoria.ul.pt - Feedback - Statistics
DeGóis
Promotores do RCAAP   Financiadores do RCAAP

Fundação para a Ciência e a Tecnologia Universidade do Minho   Governo Português Ministério da Educação e Ciência PO Sociedade do Conhecimento (POSC) Portal oficial da União Europeia