4 YEAR PhD IN NEUROSCIENCE
Cell and Developmental Biology, The Rockefeller Building, UCL
Brain Development: Cortical Intereuron Migration
The neocortex is the part of the brain involved in high-level cognitive functions and its expansion is regarded as a major evolutionary modification that led to the emergence of intelligence. These processes are achieved through circuits comprised of two classes of neurons organised in layers: excitatory pyramidal neurons and inhibitory interneurons.
Perturbations in the development of these cortical circuits can lead to neurological disorders. Recent studies indicate a role for interneurons in the neuropathology and development of epilepsy, schizophrenia, autism and mental retardation. Thus, understanding the molecular mechanisms that control the generation and migration of interneurons and their roles in cortical function is of significant clinical relevance and therapeutic importance.
Our current studies focus on exploring the functions of molecules involved in forebrain interneuron migration, specifically several classes of chemorepulsive ligands and their receptors. Examples of such molecules include Slit-Robo and Semaphorin/Neuropilin-Plexin families as well as some of their downstream signalling partners (e.g. Limk2). We have also recently carried out microarray studies which identified candidate novel molecules that showed differential expression between dorsal and ventral forebrain, as well as between different cortical interneuron streams, suggesting these novel genes may play distinct roles in interneuron migration either within specific forebrain compartments or within distinct migratory streams. In our studies, we utilise transgenic mouse lines as well as loss- and gain-of-function approaches in brain slice and explant cultures.
Blood vessel secreted molecules in cortical interneuron migration.
Identify novel downstream components of cell signalling pathways involved in interneuron migration. Examine the role of cell surface receptor molecules on cortical interneuron migratory stream specification.
Faux, C., Rakic, S., Andrews, W., Yanagawa, Y., Obata, K. and Parnavelas, J.G. (2010) Differential gene expression in migrating cortical interneurons during mouse forebrain development. Journal of Comparative Neurology 518: 1232-1248.
Hernández-Miranda, L.R., Cariboni, A., Faux, C., Ruhrberg, C., Cho, J.H., Cloutier, J.F., Eickholt, B.J., Parnavelas, J.G. and Andrews, W.D. (2011) Robo1 regulates semaphorin signaling to guide the migration of cortical interneurons through the ventral forebrain. Journal of Neuroscience 31: 6174-6187.
Antypa, M., Faux, C., Eichele, G., Parnavelas, J.G. and Andrews, W.D. (2011) Differential gene expression in migratory streams of cortical interneurons. European Journal of Neuroscience 34: 1584-1594.
Andrews, W.D., Zito, A., Memi, F., Jones, G., Tamamaki, N. and Parnavelas, J.G. (2013) Limk2 mediates semaphorin signalling in cortical interneurons migrating through the subpallium. Biology Open 2: 277-282.