Tesis doctoral de Ana Raquel Viegas Tomás
Limb outgrowth is controlled by a specialized group of cells called the apical ectodermal ridge (aer), a thickening of the limb epithelium, at its distal tip. This specialized thickening of ectodermal cells is responsible for maintaining the underlying mesenchymal cells in an undifferentiated and proliferative state, and its structure is preserved through a fine-tuned balance between proliferation and apoptosis. This equilibrium is genetically controlled but little is known about the molecules involved in this process. Several authors have been shown that both fibroblast growth factor (fgf) and erk pathway activation are crucial for aer function. Recently, flrt3, a transmembrane protein able to interact with fgf receptors, has been implicated in the triggering of erk activity by fgfs. In this thesis, we show that flrt3 expression is restricted to the aer, co-localizing its expression with fgf8 and perk activity. Loss-of-function studies demonstrate that silencing of flrt3 affects the integrity of the aer and, subsequently, its proper function during limb bud outgrowth. Our data also indicate that flrt3 expression is not regulated by fgf activity in the aer, whereas ectopic wnt3a is able to induce flrt3 expression. Overall, our findings confirm flrt3 as a key player during chicken limb development, being necessary but not sufficient for proper aer formation and maintenance under the control of bmp and wnt signalling. during limb bud development, aer structure is maintained through a fine-tuned balance between proliferation and programmed cell death and this equilibrium is genetically controlled, although little is known about the molecules involved in that process. in this thesis we present evidences involving oct4, required to establish and maintain the pluripotent cell population necessary for embryogenesis in mouse and human, in the control of the proliferative balance within the aer cells. Overexpression of otc4 in the limb ectoderm disrupts the ratio apoptosis/proliferation and, moreover, oct4 expression is under the control of wnt-canonical pathway. We also describe a special localization and behaviour of proliferating cells in the aer in response to oct4 activity. We, therefore, describe a role for oct4 as a factor able to maintain a niche of cells that is responsible for the renewal of the aer.
Datos académicos de la tesis doctoral «Apical ectodermal ridge (aer) activity and limb outgrowth during vertebrate limb development«
- Título de la tesis: Apical ectodermal ridge (aer) activity and limb outgrowth during vertebrate limb development
- Autor: Ana Raquel Viegas Tomás
- Universidad: Pompeu fabra
- Fecha de lectura de la tesis: 11/01/2010
Dirección y tribunal
- Director de la tesis
- Joaquin Rodriguez Leon
- Tribunal
- Presidente del tribunal: cristina Pujades corbi
- domingos Henrique (vocal)
- (vocal)
- (vocal)