Organization of pioneer retinal axons within the optic tract of the rhesus monkey

Retinal ganglion cell axons must make a decision at the embryonic optic chiasm to grow into the appropriate optic tract. To gain insight into the cues that play a role in sorting out the crossed from the uncrossed optic axons, we investigated the sequence of their initial ingrowth in rhesus monkey embryos. Two carbocyanine dyes, 1,1\u27-dioctadecyl-3,3,3\u27,3\u27- tetramethylindocarbocyanine perchlorate and 4-(4-dihexadecylaminostyryl)-N- methylpyridinium iodide, were placed, respectively, into the left and right retinas to identify the course of uncrossed and crossed retinal axons through the optic chiasm and tract. Our results show that at embryonic day 36 the most advanced retinal projections are uncrossed. At this age the leading crossed axons are just reaching the chiasmatic midline, whereas the uncrossed fibers have already entered the optic tract. This indicates that the pathfinding of these pioneer uncrossed fibers does not require the presence of retinal axons from the opposite eye. At subsequent stages of development (embryonic days 40 and 42) there is a clear partial segregation of the uncrossed and crossed retinal axons within the optic tract: the uncrossed- component course is in the deeper portion of the optic tract, whereas the crossed component lies in a more superficial region. Thus, the spatial organization of retinal axons within the primordial optic tract reflects the sequential addition of the uncrossed and crossed retinal fibers. The orderly and sequential ingrowth of these pioneer retinal axons indicates that specific chiasmatic cues are expressed early in development and that such pioneer fibers may serve as guides for the later-arriving retinal fibers

Specificity of retinal ganglion cell projections in the embryonic rhesus monkey.

Recent studies dealing with the organization of retinal projections in the developing rhesus monkey brain have revealed a high degree of developmental specificity. This is demonstrated by the ingrowth patterns of the initial contingents of crossed and uncrossed fibers that form the primordial optic tract as well as by the adult-like nasotemporal retinal decussation pattern evident even before the period of ganglion cell death. On the basis of these observations, it is suggested that early generated retinal fibers are guided through the optic chiasm by a transiently expressed decussation signal, and that later generated fibers utilize retinal position-dependent cues to innervate the appropriate hemisphere. Furthermore, the first retinal fibers to arrive at the dorsal lateral geniculate nucleus invade only the presumed parvocellular layers. Thus, the initial innervation of the lateral geniculate nucleus appears to reflect the birth order of retinal ganglion cell classes. It is suggested that the high degree of precision evident in the macaque monkey nasotemporal retinal decussation pattern relates to the adultlike distribution of callosal projection neurons in the developing striate cortex of the primate.Abstract Recent studies dealing with the organization of retinal projections in the developing rhesus monkey brain have revealed a high degree of developmental specificity. This is demonstrated by the ingrowth patterns of the initial contingents of crossed and uncrossed fibers that form the primordial optic tract as well as by the adult-like nasotemporal retinal decussation pattern evident even before the period of ganglion cell death. On the basis of these observations, it is suggested that early generated retinal fibers are guided through the optic chiasm by a transiently expressed decussation signal, and that later generated fibers utilize retinal position-dependent cues to innervate the appropriate hemisphere. Furthermore, the first retinal fibers to arrive at the dorsal lateral geniculate nucleus invade only the presumed parvocellular layers. Thus, the initial innervation of the lateral geniculate nucleus appears to reflect the birth order of retinal ganglion cell classes. It is suggested that the high degree of precision evident in the macaque monkey nasotemporal retinal decussation pattern relates to the adultlike distribution of callosal projection neurons in the developing striate cortex of the primate

Specificity of retinal ganglion cell projections in the embryonic rhesus monkey

Recent studies dealing with the organization of retinal projections in the developing rhesus monkey brain have revealed a high degree of developmental specificity. This is demonstrated by the ingrowth patterns of the initial contingents of crossed and uncrossed fibers that form the primordial optic tract as well as by the adult-like nasotemporal retinal decussation pattern evident even before the period of ganglion cell death. On the basis of these observations, it is suggested that early generated retinal fibers are guided through the optic chiasm by a transiently expressed decussation signal, and that later generated fibers utilize retinal position-dependent cues to innervate the appropriate hemisphere. Furthermore, the first retinal fibers to arrive at the dorsal lateral geniculate nucleus invade only the presumed parvocellular layers. Thus, the initial innervation of the lateral geniculate nucleus appears to reflect the birth order of retinal ganglion cell classes. It is suggested that the high degree of precision evident in the macaque monkey nasotemporal retinal decussation pattern relates to the adultlike distribution of callosal projection neurons in the developing striate cortex of the primate. © 1996 OPA (Overseas Publishers Association) Amsterdam B.V. Published in The Netherlands under license by Gordon and Breach Science Publishers SA

Specificity of retinal ganglion cell projections in the embryonic rhesus monkey.

Recent studies dealing with the organization of retinal projections in the developing rhesus monkey brain have revealed a high degree of developmental specificity. This is demonstrated by the ingrowth patterns of the initial contingents of crossed and uncrossed fibers that form the primordial optic tract as well as by the adult-like nasotemporal retinal decussation pattern evident even before the period of ganglion cell death. On the basis of these observations, it is suggested that early generated retinal fibers are guided through the optic chiasm by a transiently expressed decussation signal, and that later generated fibers utilize retinal position-dependent cues to innervate the appropriate hemisphere. Furthermore, the first retinal fibers to arrive at the dorsal lateral geniculate nucleus invade only the presumed parvocellular layers. Thus, the initial innervation of the lateral geniculate nucleus appears to reflect the birth order of retinal ganglion cell classes. It is suggested that the high degree of precision evident in the macaque monkey nasotemporal retinal decussation pattern relates to the adultlike distribution of callosal projection neurons in the developing striate cortex of the primate.Abstract Recent studies dealing with the organization of retinal projections in the developing rhesus monkey brain have revealed a high degree of developmental specificity. This is demonstrated by the ingrowth patterns of the initial contingents of crossed and uncrossed fibers that form the primordial optic tract as well as by the adult-like nasotemporal retinal decussation pattern evident even before the period of ganglion cell death. On the basis of these observations, it is suggested that early generated retinal fibers are guided through the optic chiasm by a transiently expressed decussation signal, and that later generated fibers utilize retinal position-dependent cues to innervate the appropriate hemisphere. Furthermore, the first retinal fibers to arrive at the dorsal lateral geniculate nucleus invade only the presumed parvocellular layers. Thus, the initial innervation of the lateral geniculate nucleus appears to reflect the birth order of retinal ganglion cell classes. It is suggested that the high degree of precision evident in the macaque monkey nasotemporal retinal decussation pattern relates to the adultlike distribution of callosal projection neurons in the developing striate cortex of the primate

Transient Alterations In Granule Cell Proliferation, Apoptosis And Migration In Postnatal Developing Cerebellum Of Crmp1\u3csup\u3e-/-\u3c/sup\u3e Mice

Collapsin response mediator proteins (CRMPs) consist of five homologous cytosolic proteins that participate in signal transduction involved in a variety of physiological events. CRMP1 is highly expressed during brain development; however, its functions remains unclear. To gain insight into its function, we generated CRMP1-/- mice with a knock-in LacZ gene. No gross anatomical changes or behavioral alterations were observed. Expression of CRMP1 was examined by the expression of the knocked-in LacZ gene, in situ hybridization with riboprobes and by imunohistochemistry. CRMP1 was found to be highly expressed in the developing the cerebellum, olfactory bulbs, hypothalamus and retina. In adults, expression level was high in the olfactory bulbs and hippocampus but very low in the retina and cerebellum and undetectable in hypothalamus. To study potential roles of CRMP1, we focused on cerebellum development. CRMP1-/- mice showed a decrease in the number of granule cells migrating out of explants of developing cerebellum, as did treatment of the explants from normal mice with anti-CRMP1 specific antibodies. CRMP1-/- mice showed a decrease in granule cell proliferation and apoptosis in external granule cell layers in vivo. Adult cerebellum of CRMP1-/- did not show any abnormalities. © 2006 The AuthorsJournal compilation © 2006 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd

Early divergence of magnocellular and parvocellular functional subsystems in the embryonic primate visual system

In both human and Old World primates visual information is conveyed by two parallel pathways: the magnocellular (M) and parvocellular (P) streams that project to separate layers of the lateral geniculate nucleus and are involved primarily in motion and color/form discrimination. The present study provides evidence that retinal ganglion cells in the macaque monkey embryo diverge into M and P subtypes soon after their last mitotic division and that optic axons project directly and selectively to either the M or P moieties of the developing lateral geniculate nucleus. Thus, initial M projections from the eyes overlap only in prospective layers 1 and 2, whereas initial P projections overlap within prospective layers 3-6. We suggest that the divergence of the M and P pathways requires developmental mechanisms different from those underlying competition-driven segregation of initially intermixed eye-specific domains in the primate visual system

Transcriptional regulation of CRMP5 controls neurite outgrowth through Sox5

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VEGF counteracts amyloid-β-induced synaptic dysfunction

International audienceThe vascular endothelial growth factor (VEGF) pathway regulates key processes in synapse function, which are disrupted in early stages of Alzheimer's disease (AD) by toxic-soluble amyloid-beta oligomers (Aβo). Here, we show that VEGF accumulates in and around Aβ plaques in postmortem brains of patients with AD and in APP/PS1 mice, an AD mouse model. We uncover specific binding domains involved in direct interaction between Aβo and VEGF and reveal that this interaction jeopardizes VEGFR2 activation in neurons. Notably, we demonstrate that VEGF gain of function rescues basal synaptic transmission, long-term potentiation (LTP), and dendritic spine alterations, and blocks long-term depression (LTD) facilitation triggered by Aβo. We further decipher underlying mechanisms and find that VEGF inhibits the caspase-3-calcineurin pathway responsible for postsynaptic glutamate receptor loss due to Aβo. These findings provide evidence for alterations of the VEGF pathway in AD models and suggest that restoring VEGF action on neurons may rescue synaptic dysfunction in AD

Disrupted surface cross-talk between NMDA and Ephrin-B2 receptors in anti-NMDA encephalitis.

International audienceAutoimmune synaptic encephalitides are recently described human brain diseases leading to psychiatric and neurological syndromes through inappropriate brain-autoantibody interactions. The most frequent synaptic autoimmune encephalitis is associated with autoantibodies against extracellular domains of the glutamatergic N-methyl-d-aspartate receptor, with patients developing psychotic and neurological symptoms in an autoantibody titre-dependent manner. Although N-methyl-d-aspartate receptors are the primary target of these antibodies, the cellular and molecular pathway(s) that rapidly lead to N-methyl-d-aspartate receptor dysfunction remain poorly understood. In this report, we used a unique combination of high-resolution nanoparticle and bulk live imaging approaches to demonstrate that anti-N-methyl-d-aspartate receptor autoantibodies from patients with encephalitis strongly alter, in a time-dependent manner, the surface content and trafficking of GluN2-NMDA receptor subtypes. Autoantibodies laterally displaced surface GluN2A-NMDA receptors out of synapses and completely blocked synaptic plasticity. This loss of extrasynaptic and synaptic N-methyl-d-aspartate receptor is prevented both in vitro and in vivo, by the activation of EPHB2 receptors. Indeed, the anti-N-methyl-d-aspartate receptor autoantibodies weaken the interaction between the extracellular domains of the N-methyl-d-aspartate and Ephrin-B2 receptors. Together, we demonstrate that the anti-N-methyl-d-aspartate receptor autoantibodies from patients with encephalitis alter the dynamic retention of synaptic N-methyl-d-aspartate receptor through extracellular domain-dependent mechanism(s), shedding new light on the pathology of the neurological and psychiatric disorders observed in these patients and opening possible new therapeutic strategies

A vital role of tubulin-tyrosine-ligase for neuronal organization.

http://www.pnas.org/content/102/22/7853.longInternational audienceTubulin is subject to a special cycle of detyrosination/tyrosination in which the C-terminal tyrosine of alpha-tubulin is cyclically removed by a carboxypeptidase and readded by a tubulin-tyrosine-ligase (TTL). This tyrosination cycle is conserved in evolution, yet its physiological importance is unknown. Here, we find that TTL suppression in mice causes perinatal death. A minor pool of tyrosinated (Tyr-)tubulin persists in TTL null tissues, being present mainly in dividing TTL null cells where it originates from tubulin synthesis, but it is lacking in postmitotic TTL null cells such as neurons, which is apparently deleterious because early death in TTL null mice is, at least in part, accounted for by a disorganization of neuronal networks, including a disruption of the cortico-thalamic loop. Correlatively, cultured TTL null neurons display morphogenetic anomalies including an accelerated and erratic time course of neurite outgrowth and a premature axonal differentiation. These anomalies may involve a mislocalization of CLIP170, which we find lacking in neurite extensions and growth cones of TTL null neurons. Our results demonstrate a vital role of TTL for neuronal organization and suggest a requirement of Tyr-tubulin for proper control of neurite extensions