Domingos, Pedro Manuel Dias Neto; (2001) The Wnt/β-catenin signalling pathway and anterior/posterior patterning in the vertebrate central nervous system. Doctoral thesis (Ph.D), UCL (University College London).

Text The_Wnt[beta]-catenin_signall.pdf Download (7MB)

Abstract

The classical Nieuwkoop's "activation/transformation" model proposes two phases of signalling for the generation of anterior/posterior (A/P) pattern in the vertebrate central nervous system (CNS). In an initial "activation" phase a neuralising signal induces neural tissue with an anterior identity (forebrain). This is followed by a "transformation" phase, where subsequent signals confer a more posterior character (midbrain, hindbrain, and spinal cord) to the neuralised tissue. In order to identify factors that may be involved in the process of posteriorisation, a functional screen in Xenopus animal cap explants was performed. By injecting noggin RNA, which induces anterior neural tissue, together with pools of RNA from a chick somite cDNA library, 1 searched for clones encoding factors capable of posteriorising the noggin injected animal caps. This strategy led to the isolation of clones encoding truncated forms of β-catenin. This molecule induced posterior neural and dorsal mesodermal markers in animal caps neuralised with Noggin. Similar results were obtained with members of the Wnt family, including Xwnt-8 and Xwnt-3a. To investigate whether the induction of posterior neural markers by the activation of the Wnt/β-catenin signalling pathway is dependent of mesoderm induction, I performed experiments using a chimeric and inducible form of β-catenin (GR- LEFΔNβCTA). Activation of this protein during blastula stages resulted in the induction of posterior neural and mesodermal markers. In contrast, during gastrula stages the activated form of the protein induced posterior neural markers in the absence of mesoderm, indicating that posteriorisation of neural tissue by β-catenin is independent of mesoderm formation. I further investigated the mechanism of induction of posterior neural markers by the Wnt/β-catenin signalling pathway. The results point to an indirect and non-cell autonomous mechanism, where cell-to-cell contact is required. Finally, I show evidence suggesting that the induction of posterior neural markers by the Wnt/β- catenin signalling pathway requires FGF signalling.

Download activity - last month

Export as XMLCSVJSON

Download activity - last 12 months

Export as XMLCSVJSON

Downloads by country - last 12 months

Export as JSONCSVXML

Archive Staff Only

View Item