Project 6:
How do interneurons find their correct location in the developing cortex?
Cortical neural circuits are comprised of two classes of neurons: the excitatory pyramidal neurons and inhibitory interneurons. These neurons are generated in different parts of the brain and utilize various modes of migration to travel vast distances to a final destination. Abnormal development of neuronal number, position and function has been implicated in neurodevelopmental and psychiatric disorders such as autism spectrum disorder, epilepsy and schizophrenia. By investigating two essential stages of development: (1) early-phase migration at the start of corticogenesis and (2) late-phase positioning and arborization, we can discover the molecular and cellular mechanisms orchestrating cortical lamination. We have used high resolution real-time imaging of migrating neurons in cortical slice cultures to identify novel signaling pathways regulating directional migration of interneurons. In combination with transplantation and advanced labeling techniques, we aim to understand the circumstances underlying successful migration and integration into functional circuits.
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Publications
Valcanis, H. and Tan, S-S (2003)
Layer specification of transplanted interneurons in developing mouse neocortex.
J. Neurosci. 23:5113-5122
Britto, J.M., Obata, K., Yanagawa, Y. and Tan, S-S (2006). Migratory response of interneurons to different regions of the developing cortex.
Cereb. Cortex 16:157-163
Hammond, V., Britto, J., So, E., Cate, H., and Tan, S-S (2007)
Control of cortical neuron migration and layering – lessons from Reelin chimeras
In “Cortical development: genes and genetic abnormalities” Novartis Foundation Symposium 288 pages 99-108 Voss, A.K., Britto, J.M., Dixon, M.P., Sheikh, B.N., Collin, C., Tan, S-S., Thomas, T. (2008)
C3G regulates cortical neuron migration, preplate splitting and radial glial cell attachment.
Development 135:2139-2149
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