Gallo G and Letourneau PC (1999), Axon guidance: A balance of signals sets axons ...

XB-ART-12754

Curr Biol 1999 Jul 01;913:R490-2. doi: 10.1016/s0960-9822(99)80304-2.

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Axon guidance: A balance of signals sets axons on the right track.

Gallo G , Letourneau PC .

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Axon guidance depends on the transduction of extracellular guidance cues into motile responses by the axonal growth cone. Recent studies in vivo have elucidated mechanisms required for this process that involve kinases and phosphatases, calcium dynamics and remodeling of the actin cytoskeleton.

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Species referenced: Xenopus
Genes referenced: abl1 actl6a enah pfn1

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Figure 1 (a) A balance of phosphatase and kinase activity regulates the guidance of Drosophila ISNb axons. In wild-type embryos, the ISNb axons (red) defasciculate from the ISN and innervate ventral muscles (blue). In the stalled phenotype, the ISNb axons do not arrive at the distal-most muscle targets. In the ISNb-bypass phenotype, the ISNb axons do not defasciculate and continue growing along the ISN. (b) In Xenopus embryos, the frequency of intracellular calcium transients in spinal cord growth cones correlates with the behavior of the growth cones during a 90° turn to fasciculate with the axons of the ventral lateral funiculus (VLF; orange). (1) While axons grow towards the VLF, their growth cones exhibit a low frequency of calcium transients and a fast rate of growth. (2) Upon contact with the VLF, growth cones stall and exhibit a high frequency of calcium transients. (3) Following turning and fasciculation with the axons of the VLF, growth cones resume a fast rate of growth and exhibit a low frequency of calcium transients.

Figure 2 (a) Immunofluorescence image of a growth cone in which the actin filaments are stained red and microtubules green. (b) Diagram of the relationships between elements of the growth-cone guidance system. The transmembrane receptor phosphatase Dlar may alter profilin activity via Ena. The activity of profilin – and possibly Ena – in turn could regulate the dynamics and structure of the actin cytoskeleton. Abl may downregulate the activity of Dlar and Ena. Transmembrane receptors may regulate growth cone calcium transients by affecting the entry of calcium into the cytoplasm through either membrane calcium channels or by release from intracellular stores (such as the endoplasmic reticulum or mitochondria). Calcium entering the cytoplasm through membrane channels may also activate release of additional calcium from intracellular stores. Calcium could regulate the structure and dynamics of the actin cytoskeleton either directly or indirectly though a number of calcium-dependent actin-binding proteins.