Philip Washbourne

Associate Professor, Department of Biology
Member, ION

Ph.D. Universita di Padova, Italy
B.Sc. Imperial College London, UK

334D Huestis


Research Interests: Molecular mechanisms of synapse formation

Overview: Information is exchanged between neurons at synapses, which are essentially specialized sites of cell-cell adhesion . A mature synapse is defined as an accumulation of synaptic vesicles within the axon, in close apposition to a dendritic membrane studded with receptors (see figure)which are held in place by a submembranous scaffold (Sheng and Kim, 2002). The formation of such an intercellular structure requires spatially and temporally controlled changes in morphology and molecular content at sites of contacts. Recent advances in subcellular fluorescence microscopy have revealed that this process involves the rapid recruitment and stabilization of both pre- and postsynaptic elements. These studies have shown that major components of the synaptic vesicle and active zone machinery travel in clusters together with other presynaptic proteins, such as calcium channels, and are rapidly recruited to new sites of contact (Ahmari et al., 2000; Zhai et al., 2001; Washbourne et al., 2002) .

On the postsynaptic side, receptor subunits and components of the scaffold or post-synaptic density (PSD) are recruited separately and with distinct time courses within minutes to hours after initial contact (Friedman et al., 2000; Bresler et al., 2001; Washbourne et al., 2002; Bresler et al., 2004)

Despite these advances the basic mechanisms by which synapse formation is induced at discrete locations and by which the molecular machinery is recruited to sites of contact remain elusive. We are currently using both mammalian primary neuronal cultures and zebrafish embryos to investigate molecules that are involved in the mechanisms of synapse formation. Techniques currently employed are live confocal imaging of fluorescently-tagged synaptic components, electron microscopy, biochemistry and molecular biology.


Related Articles

Late onset of Synaptotagmin 2a expression at synapses relevant to social behavior.

J Comp Neurol. 2020 Dec 08;:

Authors: Goode C, Voeun M, Ncube D, Eisen J, Washbourne P, Tallafuss A

As they form, synapses go through various stages of maturation and refinement. These steps are linked to significant changes in synaptic function, potentially resulting in emergence and maturation of behavioral outputs. Synaptotagmins are calcium-sensing proteins of the synaptic vesicle exocytosis machinery, and changes in Synaptotagmin proteins at synapses have significant effects on vesicle release and synaptic function. Here, we examined the distribution of the synaptic vesicle protein Synaptotagmin 2a (Syt2a) during development of the zebrafish nervous system. Syt2a is widely distributed throughout the midbrain and hindbrain early during larval development but very weakly expressed in the forebrain. Later in development, Syt2a expression levels in the forebrain increase, particularly in regions associated with social behavior, and most intriguingly, around the time social behavior becomes apparent. We provide evidence that Syt2a localizes to synapses onto neurons implicated in social behavior in the ventral forebrain and show that Syt2a is colocalized with tyrosine hydroxylase, a biosynthetic enzyme in the dopamine pathway. Our results suggest a developmentally important role for Syt2a in maturing synapses in the forebrain, coinciding with the emergence of social behavior.

PMID: 33491202 [PubMed - as supplied by publisher]

Correction: yippee like 3 (ypel3) is a novel gene required for myelinating and perineurial glia development.

PLoS Genet. 2020 Oct;16(10):e1009156

Authors: Blanco-Sánchez B, Clément A, Stednitz SJ, Kyle J, Peirce JL, McFadden M, Wegner J, Phillips JB, Macnamara E, Huang Y, Adams DR, Toro C, Gahl WA, Malicdan MCV, Tifft CJ, Zink EM, Bloodsworth KJ, Stratton KG, Undiagnosed Diseases Network, Koeller DM, Metz TO, Washbourne P, Westerfield M

[This corrects the article DOI: 10.1371/journal.pgen.1008841.].

PMID: 33104717 [PubMed - as supplied by publisher]