4 YEAR PhD IN NEUROSCIENCE
Department of Cell and Developmental Biology
Axon guidance and synapse formation
The formation of functional synaptic connections is fundamental to normal brain function. In recent years, great progress has been made on understanding how axons navigate in search for their synaptic targets. However, much less is known about the mechanisms that regulate the terminal arborization of neurons and the assembly of synapses. Our lab studies the function of signalling factors in neurite behavior and synapse formation in the vertebrate nervous system. We are particularly interested in elucidating the role of Wnt signalling molecules in the formation of neuronal connections and how this function translates into neuronal function. Our lab has demonstrated that Wnt factors regulate a number of cellular processes from axon remodeling, dendritic morphogenesis and the assembly of synapses. We are currently examining the mechanisms by which Wnt signaling regulates presynaptic assembly and how this process impinges into synaptic function. We are also studying the mechanisms by which Wnts regulate axon behavior using time-lapse microscopy on axons expressing fluorescence labeled cytoskeletal molecules. We use a multidisciplinary approach that combines cell imagining, molecular genetics/transgenesis and biochemistry.
1) To study the role of Wnt signalling in the assembly of the neuromuscular synapse using the zebrafish embryo as a model system. This project is in collaboration with Dr. Simon Hughes at King’s College London.
2) To study the function of Wnt signalling in the regulation of the microtubule and actin cytoskeletons in developing axons. Fluorescently labeled molecules such a tubulin, actin and cytoskeletal proteins will be expressed in neurons. Changes in cytoskeletal dynamics and organization will be assessed by time-lapse fluorescence microscopy and advance imagining techniques.
3) To determine the role of Wnt factors in neuronal polarity. Many molecules that regulate the growth of neurites (axons and dendrites) have also been implicated in the establishment of neuronal polarity. Given the function of Wnts in axon and dendritic growth, we wish to examine the contribution of Wnt signaling in the establishment of axon and dendrite identity during early neuronal development. To study this issue, rat hippocampal neuronal cultures and cellular approaches will be used.
Ahmad-Annuar A, Ciani L, Simeonidis I, Herreros J, Fredj NB, Rosso SB, Hall A, Brickley S, and Salinas P.C. (2006)
Signaling across the synapse: a role for Wnt and Dishevelled in presynaptic assembly and neurotransmitter release.
J.Cell Biology.174: 127-139.
Salinas P.C. (2005)
Signalling at the vertebrate synapse: new roles for embryonic morphogens?
J. Neurobiology 64: 435-445.
Rosso S.B., Sussman D., Wynshaw-Boris A. and Salinas P.C. (2005)
Wnt signalling through Dishevelled, Rac and JNK regulates dendritic development.
Nature Neurosci. 8: 34-42
Ciani, L., Krylova, O., Smalley, M.J. Dale, T.C., and Salinas, P.C. (2004)
A divergent canonical WNT signalling pathway regulates microtubule dynamics: Dishevelled signals locally to stabilize microtubules.
J. Cell Biol. 164: 243-253
Krylova O., Herreros J., Cleverley K. E., Ehler E., Henriquez J. P., Hughes S. M. and Salinas P. C. (2002)
WNT-3 expressed by motoneurons, regulates terminal arborization of neurotrophin-3-responsive spinal sensory neurons.
Neuron 35: 1043-1056.
Hall A. C., Lucas F. R. and Salinas P. C. (2000)
Axonal remodelling and synaptic
Cell 100: 525-535.