Molecules in focus
Structures in focus—filopodia

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Abstract

Filopodia are thin cell surface extensions filled with tight parallel bundles of actin filaments. They are highly dynamic structures which rapidly extend and retract as well as sweep up and down and from side to side, and can be found at the leading edge of many types of motile cells such as fibroblasts and keratinocytes, as well as the growth cone tips of migrating axons. Cells appear to use filopodia to explore the extracellular matrix (ECM) and surfaces of other cells, identifying appropriate targets for adhesion or in the case of a migrating growth cone, for sensing guidance cues that enable the axon to navigate to it’s appropriate target. As well as this sensory role, filopodia have also recently been shown to play an important mechanical role in epithelial adhesion, and are likely to be key players in developmental processes that require migrating epithelial sheets to zipper and fuse to one another. Their dynamic properties as well as their tendency to be damaged or lost after fixation mean they are best analysed using live imaging techniques. As this field improves, the number of tissues in which filopodia are seen to be playing key roles is fast increasing.

Introduction

Filopodia were first seen live in 1961 by Gustafson and Wolpert in the blastula stage of sea urchin embryo development [1]. They described filopodia (although they called them pseudopods) extending from primary mesenchymal cells (PMCs) as they migrated up the interior wall of the blastocoelic cavity. These filopodia were normally 5–35 μm in length but occasionally extended up to as long as 70 μm. They were very dynamic and appeared to Gustafson and Wolpert to be exploring the substrate over which the PMCs were migrating, leading them to speculate that they were being used by the PMCs to pick up spatial information from the overlying ectoderm.

Since the 1960s these actin protrusions have been detected in more and more cell types and have been shown to play important roles in several morphogenetic processes. They are highly dynamic structures extending and retracting at a rate of approximately 10 μm/min (a speed which can more than double during periods of intense activity) [1] as well as sweeping up and down and from side to side as they search for their particular substrate, cell or diffusible target molecule. They are also however, very delicate and do not appear to survive fixation well; consequently they are best seen in studies that use live imaging.

Section snippets

Structure and formation

Filopodia appear as thin cylindrical extensions of a cells membrane. They are filled with long actin filaments organised as a tight bundle with their barbed ends (fast growing ends) pointing towards the direction of protrusion [2]; they extend through actin polymerisation at the tips of these actin filaments. In order for a cell to form filopodia it has to somehow transduce extracellular stimuli to the actin polymerisation machinery within the cell. Whether there is a general molecular

Where are they?

Filopodia can be found at the leading edge of many types of migrating cells such as fibroblasts and keratinocytes. In these motile cells, extension of filopodia from their leading edge is frequently accompanied by the extension of thin protrusive sheets of actin filaments, between adjacent filopodia, called lamellipodia or membrane ruffles. Unlike filopodia, where actin filaments are arranged in tight bundles, lamellipodia contain actin filaments organized into a dense meshwork. Both structures

Biological function

As previously mentioned, filopodia are used by many cell types as a sensing organ to explore the extracellular matrix (ECM) and surface of other cells. In the growth cones of migrating axons, filopodia sample the external environment, searching for guidance cues that will allow the growing axon to navigate over long distances and find its appropriate target.

Axons are guided by a variety of cues that can be either attractive or repulsive. These cues operate at short-range, by contact-mediated

Summary

Filopodia clearly play several critical roles during embryonic development and presumably also in adult tissues wherever cells are motile or need to signal to one another. As better live imaging strategies come to the fore, the number of cell behaviours that filopodia are known to be involved in will undoubtedly expand. We still only know the bare bones of how a filopodial protrusion is regulated at the molecular level and precisely how it is able to transduce extracellular signals and respond

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