Tesis doctoral de Monica Delia David
Proper development of the nervous system requires a precise coordination of neurogenesis and neuronal morphogenesis. Neural progenitors, exposed to specific local environmental signals that regulate their proliferation and specification, give rise to neurons. Newborn neurons start extending neuronal processes that develop into a complex arbour. This step results in the formation of synapses between axons and dendrites and the assembly of functional brain networks. Among the extracellular factors that control these processes, wnts, neurotrophins (nts) and hepatocyte growth factor (hgf) are of special interes for this work. wnts have been shown to regulate proliferation of neural precursors, neurogenesis, terminal neuronal differentiation and synaptogenesis. Classical wnt signalling involves stabilization of cytoplasmic íY-catenin and regulation of transcription by lef/tcf transcription factors. Here we demonstrated that wnt-3a and wnt-3 signalling through the canonical/íY-catenin pathway regulate neuronal differentiation (neurogenesis and neuritogenesis) of spinal cord neuronal precursors. nts and hgf belong to different growth factor families signalling through receptor tyrosine kinase (rtk) that are important regulators of neuron survival and differentiation. In this work we showed the involvement of íY-catenin tyrosine phosphorylation downstream of nts and hgf signalling during the regulation of axon outgrowth and branching in postmitotic neurons. Nts and hgf signalling phosphorylate íY-catenin at different residues (y654 and y142, respectively). Interestingly, these differential tyrosine phosphorylations target íY-catenin to distinct subcellular locations and activate different downstream mechanisms (tcf-independent and dependent) to regulate axon morphogenesis. collectively, this work highlights the importance of íY-catenin, as a signalling component of wnt-dependent and growth factor/rtk pathways, in the control of different aspects of the neuronal differentiation.
Datos académicos de la tesis doctoral «Differentiation of spinal cord neural precursors and hippocampal neurons: a role for wnt and b-catenin«
- Título de la tesis: Differentiation of spinal cord neural precursors and hippocampal neurons: a role for wnt and b-catenin
- Autor: Monica Delia David
- Universidad: Lleida
- Fecha de lectura de la tesis: 12/03/2009
Dirección y tribunal
- Director de la tesis
- Judit Herreros Danes
- Tribunal
- Presidente del tribunal: loreta Medina hernandez
- teresa Iglesias vacas (vocal)
- carme Gallego gonzalez (vocal)
- soledad Alcantara horrillo (vocal)