We apologize to all scientists whose work could not be properly discussed and cited here due to limited space. “
“Current Opinion in Genetics & Development 2014, 27:14–19 This review comes from a themed issue on Developmental mechanisms, patterning and evolution Edited by Lee A Niswander and Lori Sussel For a

complete overview see the Issue and the Editorial Available online 8th May 2014 0959-437X/$ – see front matter, © 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.gde.2014.03.006 The homeostasis of all multicellular organisms requires active cell–cell communication, which can be achieved through direct contact or via secreted factors that travel Ibrutinib clinical trial and signal at a distance. For example, proper embryonic patterning during fetal development needs accurate

signaling orchestrated by a multitude of factors termed morphogens [1]. Furthermore, malignant cancer cells often hijack normal intercellular signaling pathways to communicate with each other and the microenvironment that serves to promote tumorigenesis and metastasis [1]. During transport, signaling molecules must face the challenges of stability and solubility in the extracellular milieu. Therefore cells have evolved a number of mechanisms to overcome these issues and to ensure that secreted factors can successfully Osimertinib price transmit information. One such mechanism involves tethering signaling molecules to membranous extracellular vesicles (EVs), which can be classified based on criteria that include cellular origin, biological function, or pathways of biogenesis [2 and 3]. First identified three decades ago in reticulocytes, exosomes are typically cup-shaped EVs with 40–100 nm diameter [4]. It is generally agreed that exosomes originate from multivesicular bodies (MVB) within the endocytic system and are released into the extracellular milieu upon the docking and fusion of the MVB with the plasma membrane [5 and 6]. The composition of exosomes

includes a broad range of molecules, such as lipid, protein, carbohydrates, DNA and RNA, reflecting their diverse biological ADAM7 functions [7 and 8]. Proteomic studies have identified a growing list of proteins that are enriched in exosomes, such as the tetraspanin molecules Cd63 and Cd81 [9 and 10]. The mechanism that meditates exosomal biogenesis remains elusive and may vary depending on cell types and functional contexts [4]. Key molecular regulators of MVB/exosomes formation and release include components of the Endosomal Sorting Complex Required for Transport (ESCRT) [11 and 12], as well as members of the Rab GTPase family (e.g. Rab11, Rab27, and Rab35) that are also important for MVB trafficking and exosome secretion [13, 14 and 15]. The stable nature and ability to travel over long distances make exosomes an ideal platform for integrating and transmitting signaling molecules between cells.