47 research outputs found
Expression and Roles of Teneurins in Zebrafish
The teneurins, also known as Ten-m/Odz, are highly conserved type II transmembrane
glycoproteins widely expressed throughout the nervous system. Functioning as
dimers, these large cell-surface adhesion proteins play a key role in regulating
neurodevelopmental processes such as axon targeting, synaptogenesis and neuronal
wiring. Synaptic specificity is driven by molecular interactions, which can occur either in
a trans-homophilic manner between teneurins or through a trans-heterophilic interaction
across the synaptic cleft between teneurins and other cell-adhesion molecules, such as
latrophilins. The significance of teneurins interactions during development is reflected in
the widespread expression pattern of the four existing paralogs across interconnected
regions of the nervous system, which we demonstrate here via in situ hybridization and
the generation of transgenic BAC reporter lines in zebrafish. Focusing on the visual
system, we will also highlight the recent developments that have been made in furthering
our understanding of teneurin interactions and their functionality, including the instructive
role of teneurin-3 in specifying the functional wiring of distinct amacrine and retinal
ganglion cells in the vertebrate visual system underlying a particular functionality. Based
on the distinct expression pattern of all teneurins in different retinal cells, it is conceivable
that the combination of different teneurins is crucial for the generation of discrete visual
circuits. Finally, mutations in all four human teneurin genes have been linked to several
types of neurodevelopmental disorders. The opportunity therefore arises that findings
about the roles of zebrafish teneurins or their orthologs in other species shed light on
the molecular mechanisms in the etiology of such human disorders
Perturbations of MicroRNA Function in Mouse Dicer Mutants Produce Retinal Defects and Lead to Aberrant Axon Pathfinding at the Optic Chiasm
During development axons encounter a variety of choice points where they have to make appropriate pathfinding decisions. The optic chiasm is a major decision point for retinal ganglion cell (RGC) axons en route to their target in order to ensure the correct wiring of the visual system. MicroRNAs (miRNAs) belong to the class of small non-coding RNA molecules and have been identified as important regulators of a variety of processes during embryonic development. However, their involvement in axon guidance decisions is less clear.We report here that the early loss of Dicer, an essential protein for the maturation of miRNAs, in all cells of the forming retina and optic chiasm leads to severe phenotypes of RGC axon pathfinding at the midline. Using a conditional deletion approach in mice, we find in homozygous Dicer mutants a marked increase of ipsilateral projections, RGC axons extending outside the optic chiasm, the formation of a secondary optic tract and a substantial number of RGC axons projecting aberrantly into the contralateral eye. In addition, the mutant mice display a microphthalmia phenotype.Our work demonstrates an important role of Dicer controlling the extension of RGC axons to the brain proper. It indicates that miRNAs are essential regulatory elements for mechanisms that ensure correct axon guidance decisions at the midline and thus have a central function in the establishment of circuitry during the development of the nervous system
The molecular phylogeny of eph receptors and ephrin ligands
<p>Abstract</p> <p>Background</p> <p>The tissue distributions and functions of Eph receptors and their ephrin ligands have been well studied, however less is known about their evolutionary history. We have undertaken a phylogenetic analysis of Eph receptors and ephrins from a number of invertebrate and vertebrate species.</p> <p>Results</p> <p>Our findings indicate that Eph receptors form three major clades: one comprised of non-chordate and cephalochordate Eph receptors, a second comprised of urochordate Eph receptors, and a third comprised of vertebrate Eph receptors. Ephrins, on the other hand, fall into either a clade made up of the non-chordate and cephalochordate ephrins plus the urochordate and vertebrate ephrin-Bs or a clade made up of the urochordate and vertebrate ephrin-As.</p> <p>Conclusion</p> <p>We have concluded that Eph receptors and ephrins diverged into A and B-types at different points in their evolutionary history, such that primitive chordates likely possessed an ancestral ephrin-A and an ancestral ephrin-B, but only a single Eph receptor. Furthermore, ephrin-As appear to have arisen in the common ancestor of urochordates and vertebrates, whereas ephrin-Bs have a more ancient bilaterian origin. Ancestral ephrin-B-like ligands had transmembrane domains; as GPI anchors appear to have arisen or been lost at least 3 times.</p
Burst-Time-Dependent Plasticity Robustly Guides ON/OFF Segregation in the Lateral Geniculate Nucleus
Spontaneous retinal activity (known as “waves”) remodels synaptic connectivity to the lateral geniculate nucleus (LGN) during development. Analysis of retinal waves recorded with multielectrode arrays in mouse suggested that a cue for the segregation of functionally distinct (ON and OFF) retinal ganglion cells (RGCs) in the LGN may be a desynchronization in their firing, where ON cells precede OFF cells by one second. Using the recorded retinal waves as input, with two different modeling approaches we explore timing-based plasticity rules for the evolution of synaptic weights to identify key features underlying ON/OFF segregation. First, we analytically derive a linear model for the evolution of ON and OFF weights, to understand how synaptic plasticity rules extract input firing properties to guide segregation. Second, we simulate postsynaptic activity with a nonlinear integrate-and-fire model to compare findings with the linear model. We find that spike-time-dependent plasticity, which modifies synaptic weights based on millisecond-long timing and order of pre- and postsynaptic spikes, fails to segregate ON and OFF retinal inputs in the absence of normalization. Implementing homeostatic mechanisms results in segregation, but only with carefully-tuned parameters. Furthermore, extending spike integration timescales to match the second-long input correlation timescales always leads to ON segregation because ON cells fire before OFF cells. We show that burst-time-dependent plasticity can robustly guide ON/OFF segregation in the LGN without normalization, by integrating pre- and postsynaptic bursts irrespective of their firing order and over second-long timescales. We predict that an LGN neuron will become ON- or OFF-responsive based on a local competition of the firing patterns of neighboring RGCs connecting to it. Finally, we demonstrate consistency with ON/OFF segregation in ferret, despite differences in the firing properties of retinal waves. Our model suggests that diverse input statistics of retinal waves can be robustly interpreted by a burst-based rule, which underlies retinogeniculate plasticity across different species
Positional Cues in the Drosophila Nerve Cord: Semaphorins Pattern the Dorso-Ventral Axis
Positional cues target sensory axons to appropriate volumes of the developing nervous system independently of their synaptic partners
Dynamic Coupling of Pattern Formation and Morphogenesis in the Developing Vertebrate Retina
In this Research Article, Picker et al. show how cells in the retina get their spatial coordinates