guided cell migration requires the generation of polarized plasma membrane protrusions such as filopodia , lamellipodia , blebs and invadopodia .
although these protrusions differ structurally and in their composition , they each contribute to cell movement by pushing the leading edge forward . both axonal growth cones and endothelial tip cells display abundant filopodia protrusions ( fig .  2 ) .
their dynamic behavior of extension and retraction is reminiscent of antennae probing their environment and are generally thought to serve as environmental sensors that integrate extracellular signals during directed migration .
growth cone morphology , reflected for instance by filopodia number , has been correlated with guidance decisions at choice points and filopodia preferentially contact target cells , sometimes over long distance . in vivo experiments with titrated doses of an inhibitor of f - actin polymerization , cytochalasin b , blocked growth cone filopodia formation in grasshopper ti1 neurons and in xenopus retinal ganglion cell neurons . while pathfinding was disrupted in conditions without filopodia ,
only minor effects were seen on axonal extension , suggesting that filopodia are dispensable for growth but essential for guidance . similarly , in vitro treatment with cytochalasin b abolished glutamate - induced growth cone turning with only slight effects on neurite extension .
however , a little known study on retinal ganglion cells suggests that axon guidance can occur without filopodia . here , the authors demonstrate that growth cones extend few or no filopodia after inhibiting ena / vasp function . while axonal elongation was slowed down , retinal ganglion cell axons devoid of filopodia showed normal trajectories in vivo and growth cone navigation across several choice points was unaffected .
axonal growth cones ( a , image courtesy of isabelle brunet ) and endothelial tip cells ( b ) extend long filopodia ( arrowheads ) in the direction of migration .
scale bars , 10 m . similar to growth cones , endothelial tip cells at the leading edge of vascular sprouts produce many long filopodia that extend toward the direction of vascular growth during angiogenesis .
these filopodia express the vegf - a receptor , vegfr2 , and become misdirected and shorter upon disruption of vegf - a distribution in the mouse retina . as filopodia have been proposed to act as sensors of the extracellular milieu and endothelial cells respond to axon guidance molecules such as slits and roundabouts , netrins and unc5 receptors , semaphorins , plexins and neuropilins , and ephrins and eph receptors , it has been widely assumed that they sense and integrate pro - angiogenic and repulsive cues in tip cells to enable guided migration and stereotypic vessel patterning .
however , the role of filopodia in vessel guidance has never been proven nor questioned .
recently , work from our laboratory demonstrated that filopodia are not essential for mediating endothelial tip cell guidance . by using low concentrations of latrunculin b ( lat .
b ) , which prevents f - actin polymerization , endothelial filopodia formation was abolished in the zebrafish embryo .
live microscopy revealed that endothelial tip cells of isvs without filopodia continued to migrate along normal trajectories to form the stereotypic isv pattern and to anastomose with other tip cells . at the low concentrations of lat .
b used , tip cells were able to generate lamellipodia that provided the driving force for cell movement although at a decreased velocity .
furthermore , the induction of new vascular sprouts toward sources of ectopic vegfa165 ensued in the absence of filopodia .
in summary , our study shows that during angiogenesis , endothelial filopodia are dispensable for tip cell guidance .
this finding complements that of dwivedy et al . , who showed that filopodia are also not essential for axonal growth cone navigation and challenges the long - standing notion that filopodia are required for guided migration .
in fact , filopodia or filopodia - like structures have been ascribed many other functions .
these include facilitating cell - cell matching and epithelial sheet adherence during dorsal closure in drosophila , transmitting signals such as delta - notch and sonic hedgehog signaling between non - neighboring cells , inducing cell shape changes required for preimplantation embryonic development by providing tension and positioning nuclei in nurse cells during oogenesis in drosophila . in endothelial cells , we propose that filopodia serve as templates from which lamellipodia emerge and that both protrusive structures coordinate to allow efficient migration and expansion of new vascular sprouts .
in addition , tip cell filopodia facilitate the process of anastomosis , a process whereby tip cells meet , fuse and establish new junctions to form a connected vascular network .
thus , the mechanism(s ) by which blood vessels are guided by extracellular cues is still unresolved .
 filopodia are highly dynamic , rod - like protrusions that are found in abundance at the leading edge of migrating cells such as endothelial tip cells and at axonal growth cones of developing neurons . 
 one proposed function of filopodia is that of an environmental probe , which serves to sense guidance cues during neuronal pathfinding and blood vessel patterning . 
 however , recent studies show that tissue guidance occurs unhindered in the absence of filopodia , suggesting a dispensability of filopodia in this process . here 
 , we discuss evidence that support as well as dispute the role of filopodia in guiding the formation of stereotypic neuronal and blood vessel patterns . 
Is There a Role for Filopodia in Cell Guidance?
Filopodia are Dispensable for Tip Cell Guidance