|
|
|
| Name |
| Pereira, Paulo N G |
|
| Nationality |
| Portuguese |
| E-Mail |
| pngp@hotmail.com |
|
| 1st Degree |
| Biochemistry |
|
| University (1st Degree) |
| Universidade do Porto |
|
| About the PhD |
| Field of Research |
| Developmental signaling; Tgf-beta/Bmp signaling |
|
| Thesis Title |
| Antagonism of Nodal signaling by BMP/Smad5 prevents ectopic primitive streak formation in mice |
|
| Abstract |
| Multiple modes of regulation of the activity of Nodal are essential for anterior–posterior patterning of the epiblast and correct positioning of the primitive streak in mouse embryos. The formation of an ectopic primitive... |
| more |
| Multiple modes of regulation of the activity of Nodal are essential for anterior–posterior patterning of the epiblast and correct positioning of the primitive streak in mouse embryos. The formation of an ectopic primitive streak or streak expansion has previously been reported in mutant mice lacking Nodal antagonists. In my thesis I provide genetic evidence for antagonism of Nodal signaling by Smad5-mediated bone morphogenetic protein (Bmp) signaling, which prevents formation of an ectopic primitive streak in the mouse amnion. Ectopic Nodal signaling in this extraembryonic tissue of Smad5-deficient mouse embryos is found to induce both Nodal fast autoregulatory and slow positive feedback loops, which are normally required for primitive streak induction. The slow positive feedback loop involves Bmp4 signaling and induction of ectopic Wnt3 in amnion. Furthermore, expression of Nodal antagonists secreted from the anterior visceral endoderm, and of Lefty2, is unchanged in the Smad5 mutant indicating that, indeed, there is an alternative Bmp/Smad5-dependent mechanism of regulation of Nodal signaling/expression in amnion. In addition, biochemical analysis in cultured cells demonstrated that Bmp4-induced Smad5-Smad2 heteromerization, which is an unconventional combination of receptor-regulated Smad proteins, antagonizes Nodal signaling by interfering with the Nodal-Smad2/4-FoxH1 (autoregulatory) pathway. In conclusion, in this study it was shown that Bmp/Smad5 signaling is essential for maintaining amnion fate and that its disruption leads to ectopic primitive streak formation. |
| close |
|
|
| Supervisor(s) |
| An Zwijsen |
|
| Co-Supervisor(s) |
| Danny Huylebroeck |
|
| University |
| Katholieke Universiteit Leuven |
|
| Laboratory |
| Laboratory of Developmental Signaling , VIB11 Center for the Biology of Disease and KUL Department for Human Genetics |
|
| City |
| Leuven |
|
| Country |
| Belgium |
|
| Date of Thesis Defence |
| 2011-06-17 |
|
| After the PhD (Current Situation) |
| Position |
| Post-Doctoral Fellow |
|
| Project |
| Role of novel CHEP12 growth factor in the generation of cardiac tissue from ES cells |
|
| Institution |
| Centre for Molecular and Structural Biomedicine (CBME), Algarve University |
|
| City |
| Faro |
|
| Country |
| Portugal |
|
|
| Relevant Publications |
|
| Pereira PNG, Dobreva MP, Graham L, Huylebroeck D, Lawson K and Zwijsen A. Amnion formation in the mouse embryo: The single amniochorionic fold model. BMC Developmental Biology, 2011 Aug 1;11:48 |
| View Publication |
|
| Moya IM, Umans L, Maas E, Pereira PNG, Beets K, Francis A, Sents W, Robertson EJ, Mummery CL, Huylebroeck D and Zwijsen A. Stalk Cell Phenotype Depends on Integration of Notch and Smad1/5 Signaling Cascades. Developmental Cell, 2012 Feb 21. |
| View Publication |
|
| Pereira PNG, Dobreva MP, Maas E, Cornelis F, Moya IM, Umans L, Verfaillie CM, Camus A, Chuva de Sousa Lopes S, Huylebroeck D and Zwijsen A. Antagonism of Nodal signaling by BMP/Smad5 prevents ectopic primitive streak formation in the mouse amnion. Development, 2012 Sept 15, 139, 3343-3354. |
| View Publication |
| Publications |
|
| REVIEW: Dobreva MP, Pereira PNG, Deprest J, Zwijsen A. On the Origin of Amniotic Stem Cells: of mice and men. International Journal of Developmental Biology, 2010, 54(5):761-77 |
| View Publication |
|
| REVIEW: Conidi A, Cazzola S, Beets K, Coddens K, Collart C, Cornelis F, Cox L, Joke D, Dobreva MP, Dries R, Esguerra C, Francis A, Ibrahimi A, Kroes R, Lesage F, Maas E, Moya I, Pereira PNG, Stappers E, Stryjewska A, van den Berghe V, Vermeire L, Verstappen G, Seuntjens E, Umans L, Zwijsen A, Huylebroeck D. Few Smad proteins and many Smad-interacting proteins yield multiple functions and action modes in TGFβ/BMP signaling in vivo. Cytokine Growth Factor, 2011 Nov 25. |
| View Publication |
|
| Dobreva MP, Lhoest L., Pereira PNG, Chuva de Sousa Lopes S, Zwijsen A and Umans L. Periostin as a Biomarker of the amniotic membrane. Stem Cells International, 2012 |
| View Publication |
| Last Update |
| 2012-04-01 09:44:23 |
| The responsibility for this page contents is entirely of the student/alumnus. |
|
 |
|
 |
|
 |
|
 |
|
 |
|
 |
|
Program financially supported by
the National Foundation for
Science and Technology
|
|
 |
|
