Queensland Brain Institute 2010 Annual Report - University of ...

Laboratory Head Dr Massimo HilliardDetermining how individual neurons develop is crucial for understandinghow highly complex neuronal structures, such as the brain and spinalcord, are formed. Dr Massimo Hilliard’s laboratory is interested inunderstanding how axons (nerve fibres conducting impulses from theneuron) and dendrites (nerve processes conducting impulses to theneuron) develop and how they are guided to their targets. The group alsoinvestigates how the axonal structure is maintained over time and how itcan be reconstituted after injury.Above: Hilliard group photo. 2010 Laboratory Members: Sean Coakley, Leonie Kirzsenblat, Jujiao Kuang, Casey Linton, Brent Neumann, DivyaPattabiraman, Katherine Truong, Nick Valmas. Above right: Neuronal polarity defects in C. elegans sensory neurons. Image Leonie Kirzsenblat.PG | 36Unlocking secrets of axonal growth and regenerationNeurons are among the most highly polarisedcells in the body, with their dendrites and axonsforming distinct morphological and functionaldomains. However, the understanding ofhow dendrites develop is poor, with only afew molecules known to play a role in thisprocess. Using the nematode – or roundworm- Caenorhabditis elegans as a model system, theHilliard group has identified two Wnt ligandsand two Frizzled receptors that regulatedendrite development in vivo.The axon protruding from a neuronal cell canextend extraordinarily long distances, withmechanisms in place to maintain the structuralintegrity of these long processes over theanimal’s lifetime. Failure in the maintenanceof the axonal process is one of the underlyingcauses of different neurodegenerativeconditions including motor neuron disease.Using forward genetic screens, researchersin the Hilliard group have identified mutantanimals in which the axons of C. elegansmechanosensory neurons and oxygen sensoryneurons spontaneously degenerate. Thegroup now seeks to identify the mutated genesresponsible for this condition, and to identifyaxonal degeneration phenotypes in motorneurons.A crucial question for neurobiologists is howsome axons can regenerate following nervedamage while others cannot. The answer willbe of great value in the treatment of neurodegenerativeconditions and traumatic nerveinjuries. Using a laser-based technology toaxotomy single neurons in living C. elegansanimals, the Hilliard laboratory has shown thataxonal regeneration can occur by a mechanismof axonal fusion, whereby the two separatedaxonal fragments can specifically re-attach andrestore the original axonal tract.Axonal degeneration in a C. elegansmechanosensory sensory neuron.Image Brent Neumann.