The trip of the tip: understanding the growth cone machinery

Abstract

Preface-The central player in the road trip of axon guidance is the growth cone, a dynamic structure located at the tip of the growing axon. During its journey, the growth cone comprises both `vehicle' and `navigator'. Whereas the `vehicle' maintains growth cone movement and provides the cytoskeletal structural elements of its framework, a motor to move forward, and a mechanism to provide traction on the road, the `navigator' aspect guides this system in a spatially-biased way to translate environmental signals into directional movement. Understanding the functions and regulation of the vehicle and navigator provides new insights into the cell biology of growth cone guidance.

The influence of receptor positioning on chemotactic information

“…These include neutrophils migrating to sites of inflammation (Downey, 1994), the slime mold Dictyostelium discoideum hunting for food (Swaney et al, 2010), and neuronal growth cones navigating to find their targets in the developing nervous system (Mortimer et al, 2008;Lowery and Van Vactor, 2009). The ability of such sensing devices to detect chemical gradients depends sensitively on unavoidable stochastic fluctuations due to the limited numbers of receptors, intracellular signalling molecules, and ligand molecules available in the gradient itself (Berg and Purcell, 1977;Bialek and Setayeshgar, 2005).…”

Analyzing neurite outgrowth from explants by fitting ellipses

“…In the past few years a large number of molecular cues have been identified which are involved in the guidance of axons and dendrites (hereafter referred to as neurites) to their targets (Tessier-Lavigne and Goodman, 1996;Dickson, 2002;Guan and Rao, 2003;Huber et al, 2003;Plachez and Richards, 2005;Mortimer et al, 2008;Lowery and Van Vactor, 2009). Crucial to both the identification and analysis of the mechanisms of action of these guidance cues have been in vitro assays (Guan and Rao, 2003;Pujic et al, 2009).…”

Using microfluidic chip to form brain-derived neurotrophic factor concentration gradient for studying neuron axon guidance

“…It is critical for the formation of correct neural circuits and nervous system function. Researches show that some of the most important cues guiding the formation of connections between neurons in the developing nervous system are molecular gradients (Masuda et al, 2012;Lowery and Van Vactor, 2009). When a growth cone migrates in a guidance cue gradient, the side of the growth cone facing higher concentrations of the cue will experience higher receptor occupancy (Tojima et al, 2011), leading to asymmetric intracellular signaling events mediated by second messengers such as Ca 2þ and cyclic nucleotides (Akiyama et al, 2009;Togashi et al, 2008).…”