Name D.M.A. van den Heuvel (Dianne)
Department Neuroscience and Pharmacology
Section Neurodevelopment
Function PhD- student
E-mail:
D.M.A.vandenHeuvel@umcutrecht.nl
tel: +31-88-7568036
Supervisor Dr. R.J. Pasterkamp
Title research Function of axon guidance receptor signalling during brain development
Summary research Mature brain function relies on the establishment of a precisely sculptured neuronal network. This network forms during embryonic development when neurons send out axons to their targets. Axons are guided along predescribed routes by attractive and repulsive cues in the extracellular environment. To help to find their way, axons are tipped with a highly motile and exquisitely sensitive structure, the growth cone. Receptor complexes at the growth cone cell surface detect guidance molecules and consequently trigger intracellular signaling cascades that infringe upon the cytoskeleton and induce growth cone/axon steering. During the past decade, a myriad of guidance cues and receptors has been characterized. In contrast, the intracellular signaling pathways involved in axon guidance are only poorly understood. Therefore, a major challenge in neurobiology today is to define the intracellular signaling mechanisms that mediate the formation of a functional neuronal network. Importantly, understanding the intracellular basis of axon guidance will help to design therapeutic strategies for treating situations of perturbed neuronal connectivity such as during disease or following injury. Therefore, the current goals of understanding axon guidance cue signaling are clear: identify missing signaling components, determine their linear and network relations, and establish the nature and extent of molecular cross-talk between axon guidance cue and other signaling cascades. We plan to further define the intracellular signaling complex downstream of several axon guidance receptors by using high- in vivo proteomics techniques, tissue and cell culture assays and mouse genetics (transgenic and knockout/knockin approaches).
PublicationsVan den Heuvel, D.M.A. and Pasterkamp, R.J. (2008). Getting connected in the dopamine system. Progress in Neurobiology (epub ahead of print).