Cell-Cell and Cell-Matrix Interactions during Axons Guidance

The establishment of neuronal connections during development is a critical process for the correct function of central nervous system and for their regeneration during adult stages. Axon extension and guidance toward their targets are a complex process involving several signals provided by extracellular milieu where secreted factors, other cells, axons, and extracellular matrix proteins are interacting to establish the wiring of the brain. The expression of those signals at specific time and space, and their mechanisms of action during axon projection are the subject of numerous studies. This knowledge had contributed to understand the complex panorama of brain wiring during development and the origin and possible cure of central nervous system diseases. In this chapter, we focus on cell-cell and cell-matrix interactions as two important signals during axon guidance, and how these interactions impact the response to diffusible guidance cues. We emphasize the need and the challenge to understand the complex relations among simultaneous signals to guide axons projections, and how this knowledge could influence approaches to deal with neural regeneration issues

La consulta previa en la Constitución del 2008

El derecho a la consulta previa se encuentra consagrado desde la Constitución de 1998. Desde su vigencia, el Estado ha venido ignorando este derecho, ya que su interés prioritario ha sido el desarrollo económico, ocasionando graves prejuicios culturales y ambientales a las comunidades indígenas y a la sociedad en general. La Constitución del 2008 amplia la protección de estos derechos colectivos pertenecientes a los pueblos y comunidades indígenas, tomando como punto de partida el hecho de introducir en el artículo primero la noción del "estado constitucional de derechos y justicia", caracterizado no solo por la extensa gama de derechos sino por la protección que se da a los mismo a través de las garantías. En la misma línea, esta nueva noción de estado, para mayor protección de los Derechos, coloca a la par tanto a las normas constitucionales como aquellas que se encuentran dentro de los instrumentos internacionales de derechos humanos y que sean más favorables a los derechos humanos. Por lo que, el derecho a la consulta previa a pesar de encontrarse determinado de una forma más explícita en nuestra actual Constitución, todavía nos deja incógnitas acerca de la aplicación y cumplimiento de este derecho, por lo que debemos recalcar que de conformidad a la Constitución ecuatoriana vigente debe ajustarse a los términos señalados a la misma, así como también al Convenio 169 de la OIT, y la Declaración de Naciones Unidas sobre los Derechos de los Pueblos Indígenas de acuerdo a lo establecido en el párrafo anterior

Ascending midbrain dopaminergic axons require descending GAD65 axon fascicles for normal pathfinding

The Nigrostriatal pathway (NSP) is formed by dopaminergic axons that project from the ventral midbrain to the dorsolateral striatum as part of the medial forebrain bundle. Previous studies have implicated chemotropic proteins in the formation of the NSP during development but little is known of the role of substrate-anchored signals in this process. We observed in mouse and rat embryos that midbrain dopaminergic axons ascend in close apposition to descending GAD65-positive axon bundles throughout their trajectory to the striatum. To test whether such interaction is important for dopaminergic axon pathfinding, we analyzed transgenic mouse embryos in which the GAD65 axon bundle was reduced by the conditional expression of the diphtheria toxin. In these embryos we observed dopaminergic misprojection into the hypothalamic region and abnormal projection in the striatum. In addition, analysis of Robo1/2 and Slit1/2 knockout embryos revealed that the previously described dopaminergic misprojection in these embryos is accompanied by severe alterations in the GAD65 axon scaffold. Additional studies with cultured dopaminergic neurons and whole embryos suggest that NCAM and Robo proteins are involved in the interaction of GAD65 and dopaminergic axons. These results indicate that the fasciculation between descending GAD65 axon bundles and ascending dopaminergic axons is required for the stereotypical NSP formation during brain development and that known guidance cues may determine this projection indirectly by instructing the pathfinding of the axons that are part of the GAD65 axon scaffold

Neurophilic Descending Migration of Dorsal Midbrain Neurons Into the Hindbrain

Stereotypic cell migrations in the developing brain are fundamental for the proper patterning of brain regions and formation of neural networks. In this work, we uncovered in the developing rat, a population of neurons expressing tyrosine hydroxylase (TH) that migrates posteriorly from the alar plate of the midbrain, in neurophilic interaction with axons of the mesencephalic nucleus of the trigeminal nerve. A fraction of this population was also shown to traverse the mid-hindbrain boundary, reaching the vicinity of the locus coeruleus (LC) in rhombomere 1 (r1). This migratory population, however, does not have a noradrenergic (NA) phenotype and, in keeping with its midbrain origin, expresses Otx2 which is down regulated upon migration into the hindbrain. The interaction with the trigeminal mesencephalic axons is necessary for the arrangement and distribution of migratory cells as these aspects are dramatically altered in whole embryo cultures upon disruption of trigeminal axon projection by interfering with DCC function. Moreover, in mouse embryos in an equivalent developmental stage, we detected a cell population that also migrates caudally within the midbrain apposed to mesencephalic trigeminal axons but that does not express TH; a fraction of this population expresses calbindin instead. Overall, our work identified TH-expressing neurons from the rat midbrain alar plate that migrate tangentially over long distances within the midbrain and into the hindbrain by means of a close interaction with trigeminal mesencephalic axons. A different migratory population in this region and also in mouse embryos revealed diversity among the cells that follow this descending migratory pathway

Logros de las comunidades, pueblos y nacionalidades indígenas en el ámbito de la interculturalidad en el Ecuador

Resumen El tema de esta monografía es central para entender cómo los pueblos indígenas han venido luchando por conseguir una necesaria construcción de la interculturalidad, gracias a su capacidad de resistencia frente a las adversidades de la colonia, de la explotación de la que han sido víctimas y del estado de exclusión y discriminación social. Esta resistencia -sofocada muchas veces por medio de la violencia de las élites dominantes-, se expresó en movimientos de rebelde protesta a lo largo de la historia (últimamente, en la década de los años noventa del siglo pasado) y permitió que los pueblos y nacionalidades indígenas preservaran y mantuvieran vigentes sus expresiones culturales: lengua, tradiciones, creencias, ritos, saberes ancestrales, etc. Para el desarrollo de este trabajo nos basaremos en dos ejes temáticos básicos: El primero es con respecto al marco histórico-cultural, en el que estableceremos las etapas que han venido atravesando las comunidades, pueblos y nacionalidades, como también las reivindicaciones logradas (nos referiremos especialmente a los derechos colectivos y a su significación). El segundo tratará sobre el importante reconocimiento del Estado ecuatoriano como plurinacional, pluricultural y multiétnico (Art. 1, inciso 1; numeral 1 del artículo 380; Art. 257, inciso1; Art. 6, inciso 2), el mismo que se encuentra plasmado en nuestra actual Constitución.Diplomado Superior en Interculturalidad. Derechos Humanos y MigraciónCuenc

Infrared Laser Effects on Cell Projection Depend on Irradiation Intermittence and Cell Activity

Highly focused near-infrared (NIR) lasers have been used to induce fibroblast and neuron protrusions in a technique called optical guidance. However, little is known about the biochemical and biophysical effects that the laser provokes in the cell and optimal protocols of stimulation have not yet been established. Using intermittent NIR laser radiation and multivariate time series representations of cell leading edge movement, we analyzed the direction and velocity of cell protrusions. We found that the orientation and advance of PC12 neuron phenotype cells and 3T3 fibroblasts protrusions remain after the laser is turned off, but the observed increase in velocity stops when radiation ceases. For an increase in the speed and distance of cell protrusions by NIR laser irradiation, the cell leading edge needs to be advancing prior to the stimulation, and NIR irradiation does not enable the cell to switch between retracting and advancing states. Using timelapse imaging of actin-GFP, we observed that NIR irradiation induces a faster recruitment of actin, promoting filament formation at the induced cell protrusions. These results provide fresh evidence to understand the phenomenon of the optical guidance of cell protrusions

LIM-homeobox gene Lhx5 is required for normal development of Cajal-Retzius cells

Cajal-Retzius (C-R) cells play important roles in the lamination of the mammalian cortex via reelin secretion. The genetic mechanisms underlying the development of these neurons have just begun to be unraveled. Here, we show that two closely related LIM-homeobox genes Lhx1 and Lhx5 are expressed in reelin+ cells in various regions in the mouse telencephalon at or adjacent to sites where the C-R cells are generated, including the cortical hem, the mantle region of the septal/retrobulbar area, and the ventral pallium. Whereas Lhx5 is expressed in all of these reelin-expressing domains, Lhx1 is preferentially expressed in the septal area and in a continuous domain spanning from lateral olfactory region to caudomedial territories. Genetic ablation of Lhx5 results in decreased reelin+ and p73+ cells in the neocortical anlage, in the cortical hem, and in the septal, olfactory, and caudomedial telencephalic regions. The overall reduction in number of C-R cells in Lhx5 mutants is accompanied by formation of ectopic reelin+ cell clusters at the caudal telencephalon. Based on differential expression of molecular markers and by fluorescent cell tracing in cultured embryos, we located the origin of reelin+ ectopic cell clusters at the caudomedial telencephalic region. We also confirmed the existence of a normal migration stream of reelin+ cells from the caudomedial area to telencephalic olfactory territories in wild-type embryos. These results reveal a complex role for Lhx5 in regulating the development and normal distribution of C-R cells in the developing forebrain. Copyright © 2010 the authors.Peer Reviewe