As they travel through the rostral migratory stream, neuroblasts are held together, probably in part by thrombospondin-1's binding to the<unk>  receptors ApoER2 and VLDLR. As they arrive to the destination, the groups are dispersed by<unk>  and cells strike out on their individual paths. A fragment of an illustration from Lennington et al., 2003. The primary functions of<unk>  are the regulation of corticogenesis and neuronal cell positioning in the prenatal period, but the protein also continues to play a role in adults.<unk>  is found in numerous tissues and organs, and one could roughly subdivide its functional roles by the time of expression and by localisation of its action. During development A number of non-nervous tissues and organs express<unk>  during development, with the expression sharply going down after organs have been formed. The role of the protein here is largely unexplored, because the knockout mice show no major pathology in these organs.<unk> 's role in the growing central nervous system has been extensively characterized. It promotes the differentiation of progenitor cells into radial glia and affects the orientation of its fibers, which serve as the guides for the migrating neuroblasts. The position of<unk> -secreting cell layer is important, because the fibers orient themselves in the direction of its higher concentration. For example,<unk>  regulates the development of layer-specific connections in hippocampus and entorhinal cortex. illustration from Nomura T. et al., 2008.<unk> -expressing cells (red) on C stimulate the growth of green glial fibers, while on B, where the red cells do not express<unk> , radial glia is more disarrayed. Mammalian corticogenesis is another process where<unk>  plays a major role. In this process the temporary layer called preplate is split into the marginal zone on the top and subplate below, and the space between them is populated by neuronal layers in the inside-out pattern. Such an arrangement, where the newly created neurons pass through the settled layers and position themselves one step above, is a distinguishing feature of mammalian brain, in contrast to the evolutionary older reptile cortex, in which layers are positioned in an "outside-in" fashion. When<unk>  is absent, like in the mutant reeler mouse, the order of cortical layering becomes roughly inverted, with younger neurons finding themselves to be unable to pass the settled layers. Subplate neurons fail to stop and invade the upper most layer, creating the so-called superplate in which they mix with Cajal-Retzius cells and some cells normally destined for the second layer. Increased<unk>  expression changes the morphology of migrating neurons: unlike the round neurons with short branches (C) they assume bipolar shape (D) and attach themselves (E) to the radial glia fibers that are extending in the direction of<unk> -expressing cells. Nomura T. et al., 2008. There is no agreement concerning the role of<unk>  in the proper positioning of cortical layers. The original hypothesis, that the protein is a stop signal for the migrating cells, is supported by its ability to induce the dissociation, its role in asserting the compact granule cell layer in the hippocampus, and by the fact that migrating neuroblasts evade the<unk> -rich areas. But an experiment in which murine corticogenesis went normally despite the malpositioned<unk>  secreting layer, and lack of evidence that<unk>  affects the growth cones and leading edges of neurons, caused some additional hypotheses to be proposed. According to one of them,<unk>  makes the cells more susceptible to some yet undescribed positional signaling cascade.<unk>  may also ensure correct neuronal positioning in the spinal cord: according to one study, location and level of its expression affects the movement of sympathetic preganglionic neurons. The protein is thought to act on migrating neuronal precursors and thus controls correct cell positioning in the cortex and other brain structures. The proposed role is one of a dissociation signal for neuronal groups, allowing them to separate and go from tangential chain-migration to radial individual migration. Dissociation detaches migrating neurons from the glial cells that are acting as their guides, converting them into individual cells that can strike out alone to find their final position. Top: Representative image of somatic<unk>  immunoreactivities found in 12-day-in-vitro hippocampal neurons. Bottom:<unk>  immunofluorescence (red) overlaid with MAP2 counterstain (green). A fragment of an illustration from Campo et al., 2009.<unk>  takes part in the developmental change of NMDA receptor configuration, increasing mobility of NR2B-containing receptors and thus decreasing the time they spend at the synapse. It has been hypothesized that this may be a part of the mechanism behind the "NR2B-NR2A switch" that is observed in the brain during its postnatal development. Ongoing<unk>  secretion by GABAergic hippocampal neurons is necessary to keep NR2B-containing NMDA receptors at a low level. In adults In the adult nervous system,<unk>  plays an eminent role at the two most active neurogenesis sites, the subventricular zone and the dentate gyrus. In some species, the neuroblasts from the subventricular zone migrate in chains in the rostral migratory stream (RMS) to reach the olfactory bulb, where<unk>  dissociates them into individual cells that are able to migrate further individually. They change their mode of migration from tangential to radial, and begin using the radial glia fibers as their guides. There are studies showing that along the RMS itself the two receptors, ApoER2 and VLDLR, and their intracellular adapter DAB1 function independently of<unk> , most likely by the influence of a newly proposed ligand, thrombospondin-1. In the adult dentate gyrus,<unk>  provides guidance cues for new neurons that are constantly arriving to the granule cell layer from subgranular zone, keeping the layer compact.<unk>  also plays an important role in the adult brain by modulating cortical pyramidal neuron dendritic spine expression density, the branching of dendrites, and the expression of long-term potentiation as its secretion is continued diffusely by the GABAergic cortical interneurons those origin is traced to the medial ganglionic eminence. In the adult organism the non-neural expression is much less widespread, but goes up sharply when some organs are injured. The exact function of<unk>  upregulation following an injury is still being researched.
Reelin
Embelin
Equilin
AmnesiA
Telokin
Basigin
Peripherin
Collectin