Purinergic Signalling (2008) 4:357–364 DOI 10.1007/s11302-008-9121-3 ORIGINAL ARTICLE Adenosine induces growth-cone turning of sensory neurons Benjamin Grau & John-Christian Eilert & Sebastian Munck & Hartmann Harz Received: 5 June 2008 / Accepted: 4 August 2008 / Published online: 6 September 2008 # The Author(s) 2008. This article is published with open access at Springerlink.com Abstract The formation of appropriate connections be- tween neurons and their specific targets is an essential step during development and repair of the nervous system. Growth cones are located at the leading edges of the growing neurites and respond to environmental cues in order to be guided to their final targets. Directional information can be coded by concentration gradients of substrate-bound or diffusible-guidance molecules. Here we show that concen- tration gradients of adenosine stimulate growth cones of sensory neurons (dorsal root ganglia) from chicken embryos to turn towards the adenosine source. This response is mediated by adenosine receptors. The subsequent signal transduction process involves cAMP. It may be speculated that the in vivo function of this response is concerned with the formation or the repair and regeneration of the peripheral nervous system. Electronic supplementary material The online version of this article (doi:10.1007/s11302-008-9121-3) contains supplementary material, which is available to authorised users. B. Grau Department of Cellular, Molecular, and Developmental Neurobiology, Cajal Institute, C.S.I.C., Ave. Dr. Arce 37, Madrid 28002, Spain J.-C. Eilert : H. Harz (*) BioImaging Zentrum der Ludwig-Maximilians-Universität München, Großhaderner Straße 2, 82152 Martinsried, Germany e-mail: harz@biz.uni-muenchen.de S. Munck Light Microscopy and Imaging Network (LiMoNe) VIB, Department of Molecular and Developmental Genetics, K.U.Leuven Campus Gasthuisberg, Herestraat 49, Box 602, 3000 Leuven, Belgium Keywords Growth cone . Guidance . DRG . Gradient . cAMP . Adenosine receptor Introduction Many guidance molecules not only control the growth direction, but also affect neurite initiation and elongation [1]. Purins are interesting in this respect as it has been shown that they are capable of promoting neurite growth [2–5] and that micro-gradients of ATP induce growth-cone turning of embryonic neurons from Xenopus [6]. Here we investigate a possible involvement of adenosine in growth- cone turning of neurons, a new function for this molecule. An example that adenosine may have new, so far unknown, cell biological functions has been recently given by Chen and colleagues [7], who showed that adenosine regulates migration speed of neutrophil cells during chemotaxis. Effects of extracellular adenosine are mediated by receptors belonging to the super family of G protein-coupled receptors [8], which also include members known to mediate growth-cone turning [9, 10]. The family of adenosine receptors comprises four subtypes, A1, A2A, A2B, and A3 [11], linked to a variety of downstream signalling pathways, both cAMP dependent and indepen- dent [12, 13]. Whereas the activation of A1 or A3 receptors decreases the intracellular cAMP concentration by inhibi- tion of the adenylate cyclase, A2A and A2B receptor activation stimulates adenylate cyclase activity and thereby increases the intracellular cAMP concentration. It is known that cAMP has an effect on growth-cone turning [14–16], thus providing a link between adenosine receptors and growth-cone turning. In order to induce changes in the growing direction, guidance cues must provide directional information detect-