Nerve growth cones, the dilated tip of developing axons, are equipped with exquisite abilities to sense environmental cues and to move rapidly through complex terrains of developing brain, leading the axons to their specific targets for precise neuronal wiring. The actin cytoskeleton is the major component of the growth cone that powers its directional motility. Past research has provided significant insights into the mechanisms by which growth cones translate extracellular signals into directional migration. In this review, we summarize the actin-based mechanisms underlying directional growth cone motility, examine novel findings, and discuss the outstanding questions concerning the actin-based growth cone behaviors.
Oligodendrocytes (OLs) insulate axonal fibers for fast conduction of nerve impulses by wrapping axons of the CNS with compact myelin membranes. Differentiating OLs undergo drastic chances in cell morphology. Bipolar oligodendroglial precursor cells (OPCs) transform into highly ramified multipolar OLs, which then expand myelin membranes that enwrap axons. While significant progress has been made in understanding the molecular and genetic mechanisms underlying CNS myelination and its disruption in diseases, the cellular mechanisms that regulate OL differentiation are not fully understood. Here, we report that developing rat OLs in culture exhibit spontaneous Ca 21 local transients (sCaLTs) in their process arbors in the absence of neurons. Importantly, we find that the frequency of sCaLTs markedly increases as OLs undergo extensive process outgrowth and branching. We further show that sCaLTs are primarily generated through a combination of Ca 21 influx through store-operated Ca 21 entry (SOCE) and Ca 21 release from internal Ca 21 stores. Inhibition of sCaLTs impairs the elaboration and branching of OL processes, as well as substantially reduces the formation of large myelin sheets in culture. Together, our findings identify an important role for spontaneous local Ca 21 signaling in OL development.
The actin cytoskeleton drives cell motility and is essential for neuronal development and function. LIM and SH3 Protein 1 (LASP1) is a unique actin-binding protein that is expressed in a wide range of cells including neurons, but its roles in cellular motility and neuronal development are not well understood. We report that LASP1 is expressed in rat hippocampus early in development, and this expression is maintained through adulthood. High-resolution imaging reveals that LASP1 is selectively concentrated at the leading edge of lamellipodia in migrating cells and axonal growth cones. This local enrichment of LASP1 is dynamically associated with the protrusive activity of lamellipodia, depends on the barbed ends of actin filaments, and requires both the LIM domain and nebulin repeats of LASP1. Knockdown of LASP1 in cultured rat hippocampal neurons results in a substantial reduction in axonal outgrowth and arborization. Finally, loss of the Drosophila homolog Lasp from a subset of commissural neurons in the developing ventral nerve cord produces defasciculated axon bundles that do not reach their targets. Together, our data support a novel role for LASP1 in actin-based lamellipodial protrusion and establish LASP1 as a positive regulator of both in vitro and in vivo axon development. [Media: see text]
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