Filopodia
Filopodia are highly dynamic, actin-rich protrusions observable on most animal cells during developmental periods of growth and migration. Work in the Smith lab dating back to the late 1980's has explored basic mechanisms of filopodial force generation and established that filopodia on both dendrites and axons play crucial roles in the developmental formation of synaptic connections and neural circuitry. The goals have been better understanding of neural circuit developmental and neural plasticity and insights that might lead to new strategies for the repair of damaged or degenerating nervous systems.

The extension-retraction dynamics typical of axonal growth-cone filopodia are evident in this time-lapse movie of an Aplysia bag cell growth cone.

See: Forscher & Smith (1988)

Small polystyrene beads landing on the surfaces of these Aplysia bag cell growth cones attach via transmembrane proteins to the underlying actin cytoskeleton and mark the retrograde flow of filamentous actin. Beads that land on filopodia move at the same velocities as those on the lamellipodial actin meshwork.

See: Forscher & Smith (1989)

A transgenically labelled retinal ganglion cell axon is seen here forming its terminal arbor in the optic tectum of a larval zebrafish shows that many highly filpodia are formed and promptly eliminated during this process. A small subset are stabilized to form the definitive synaptic arbor.

See: Hua et al. (2005) and Meyer & Smith (2006)

A transgenically labelled dendrite (red) growing in the optic tectum of a larval zebrafish shows that the selective conversion of a small subset of dynamic filopodia depends on the formation of punctatew postsynaptic specializations (green).

See: Niell, Meyer & Smith (2004)

These and many other observations regarding the mechanisms and developmental roles of neural filopodia are documented in detail in the publications listed below.

Smithlab Filopodium Bibliography

Smith, S.J. (1988) Neuronal Cytomechanics: The actin-based motility of growth cones. Science 242: 708-715.

Forscher, P. and Smith, S.J. (1988) Actions of cytochalasins on the organization of actin filaments and microtubules in a neuronal growth cone. J. Cell Biol. 107: 1505-1516. [PDF]

Forscher, P. and Smith, S.J (1989) Cytoplasmic actin filaments move particles on the surface of a neuronal growth cone. In: Optical Microscopy for Biology (K. Jacobson and Brian Hermann, Eds.), Wiley-Liss, N.Y. pp. 459-471.

Cornell-Bell, A.H., Thomas, P.G. and Smith, S.J. (1990). The excitatory neurotransmitter glutamate causes filopodia formation in cultured hippocampal astrocytes. Glia 3:322-334. [PDF]

Smith, S.J, Cooper, M.W. and Waxman, A. (1990). Laser microscopy of subcellular structure in living Neocortex: can one see dendritic spines twitch? In:The Biology of Memory, XXIII Symposium Medicum Hoechst, (L.R.Squire and E. Lindenlaub, Eds), F.K. Schattauer Verlag, Stuttgart. pp. 49-71.

Smith, S.J and Jahr, C.E. (1992) Rapid induction of filopodial sprouting by applications of glutamate to hippocampal neurons. In: The Nerve Growth Cone, (P.C. Letourneau, S.B. Kater and E.R. Macagno, Eds.), Raven Press, New York. pp. 19-26. [PDF]

Cooper, M.W. and Smith, S.J. (1992) A real-time analysis of growth cone - target cell interactions during the formation of stable contacts between hippocampal neurons in culture. J. Neurobiology, 23, 814-828.

Dailey, M. E. and Smith, S.J. (1993) Confocal imaging of mossy fiber growth in live hippocampal slices. Jap. J. Physiol. 43 (Suppl. 1), 183-192.

Dailey , M.E. , Buchanan, J., Bergles, D.E. and Smith, S.J (1994) Mossy fiber growth and synaptogenesis in rat hippocampal slices in vitro. J. Neurosci. 14: 1060-1078. [PDF]

Ryan, T.A., and Smith, S.J. (1995) Vesicle pool mobilization during action potential firing at hippocampal synapses. Neuron 14: 983-989. [PDF]

Dailey , M.E. and Smith, S.J (1996) The dynamics of dendritic structure in developing hippocampal slices. J. Neurosci. 16: 2983-2994. [PDF]

Ziv. N.E. and Smith, S.J (1996) Evidence for a role of dendritic filopodia in synaptogenesis and spine formation. Neuron 17: 91-102. [PDF]

Smith, S.J (1999) Dissecting dendrite dynamics. Science 19: 1860-1861.

Jontes, J.D., Buchanan, J. and Smith, S.J (2000) Growth cone and dendrite dynamics in zebrafish embryos: in vivo imaging of early events in synaptogenesis. Nature Neuroscience 3: 231-237. [PDF]

Jontes, J.D. and Smith, S.J (2000) Filopodia, spines and the generation of synaptic diversity. Neuron 27, 11-14. [PDF]

Ahmari, S.E. and Smith, S.J (2002) Minireview: Knowing a nascent synapse when you see it. Neuron 34: 333-336. [PDF]

Meyer, M.P., Niell, C.M, and Smith, S.J (2003) Brain Imaging: How stable are synaptic connections? Curr. Biol. 13(5):R180-2. [PDF]

Niell, C.M., Meyer, M.P and Smith, S.J (2004) In vivo imaging of synapse formation on a growing dendritic arbor. Nature Neurosci. 7: 254-260. [PDF]

Niell, C.M. and Smith, S.J (2004) Live optical imaging of nervous system develop­ment. Ann. Rev. Physiol., 66 : 771-798. [PDF]

Hua, Y and Smith, S.J (2004) Neural activity and the dynamics of central nervous system development. Nature Neurosci. 7: 327-32. [PDF]

Jontes, J.D., Emond, M.R., Smith, S.J (2004) In vivo trafficking and targeting of N-cadherin to nascent presynaptic terminals. J. Neurosci. 24(41): 9027-34. [PDF]

Hua, Y., Smear, M.C., Baier, H. and Smith, S.J (2005) Activity-Based Competition Regulates Axon Growth in Vivo. Nature 434: 1022-1026. [PDF]

Meyer, M.P., Trimmer, J.S., Gilthorpe, J.D., and Smith, S.J (2005) Characterization of Zebrafish PSD-95 Gene Family Members. J. Neurobiol. 63:91-105. [PDF]

Meyer, M.P. & Smith, S.J (2006) Evidence from in vivo imaging that synaptogenesis guides the growth and branching of axonal arbors by two distinct mechanisms. J. Neurosci. 26:3604-14. [PDF]

Niell, C.M. (2006) Theoretical analysis of a synaptotropic dendrite growth mechanism. J. Theor. Biol. (in press). [PDF]

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