David Feldheim

Ephrin-A2 and -A5 influence patterning of normal and novel retinal projections to the thalamus: conserved mapping mechan...

Published in The Journal of Comparative Neurology

Sensory axons are targeted to modality-specific nuclei in the thalamus. Retinal ganglion cell axons project retinotopically to their principal thalamic target, the dorsal lateral geniculate nucleus (LGd), in a pattern likely dictated by the expression of molecular gradients in the LGd. Deafferenting the auditory thalamus induces retinal axons to in...

Altered transcriptional patterns affecting several metabolic pathways in strains of Salmonella typhimurium which overexp...

Published in Journal of Bacteriology

Expression of beta-galactosidase in transcriptional fusions with the pps gene (encoding phosphoenolpyruvate [PEP] synthase), the aceBAK operon (encoding malate synthase, isocitrate lyase, and isocitrate dehydrogenase kinase, respectively), and the phs operon (encoding either thiosulfate reductase or a regulatory protein controlling its expression) ...

Alkaline phosphatase fusions of ligands or receptors as in situ probes for staining of cells, tissues, and embryos.

Published in G Protein Coupled Receptors - Structure

Ephrins as negative regulators of adult neurogenesis in diverse regions of the central nervous system.

Published in Proceedings of the National Academy of Sciences

In the central nervous system (CNS) of adult mammals, neurogenesis occurs in only two restricted areas, the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Isolation of multipotent progenitor cells from other CNS regions suggests that their neurogenic potential is dictated by local environmental cues. Here, we report th...

Persistence of graded EphA/Ephrin-A expression in the adult frog visual system.

Published in The Journal of Comparative Neurology

Many studies have demonstrated the involvement of the EphA family of receptor tyrosine kinases and their ligands, ephrin-A2 and -A5, in the development of the temporonasal axis of the retinotectal/collicular map, but the role of these molecules in optic nerve regeneration has not been well studied. Noting that the characteristic gradients of the Ep...

Loss-of-function analysis of EphA receptors in retinotectal mapping.

Published in Journal of Neuroscience

EphA tyrosine kinases are thought to act as topographically specific receptors in the well-characterized projection map from the retina to the tectum. Here, we describe a loss-of-function analysis of EphA receptors in retinotectal mapping. Expressing patches of a cytoplasmically truncated EphA3 receptor in chick retina caused temporal axons to have...

Stochastic Interaction between Neural Activity and Molecular Cues in the Formation of Topographic Maps.

Published in Neuron

Topographic maps in visual processing areas maintain the spatial order of the visual world. Molecular cues and neuronal activity both play critical roles in map formation, but their interaction remains unclear. Here, we demonstrate that when molecular- and activity-dependent cues are rendered nearly equal in force, they drive topographic mapping st...

Ephrin-as guide the formation of functional maps in the visual cortex.

Published in Neuron

Ephrin-As and their receptors, EphAs, are expressed in the developing cortex where they may act to organize thalamic inputs. Here, we map the visual cortex (V1) in mice deficient for ephrin-A2, -A3, and -A5 functionally, using intrinsic signal optical imaging and microelectrode recording, and structurally, by anatomical tracing of thalamocortical p...

Alignment of multimodal sensory input in the superior colliculus through a gradient-matching mechanism.

Published in Journal of Neuroscience

The superior colliculus (SC) is a midbrain structure that integrates visual, somatosensory, and auditory inputs to direct head and eye movements. Each of these modalities is topographically mapped and aligned with the others to ensure precise behavioral responses to multimodal stimuli. While it is clear that neural activity is instructive for topog...

Roles for ephrins in positionally selective synaptogenesis between motor neurons and muscle fibers.

Published in Neuron

Motor axons form topographic maps on muscles: rostral motor pools innervate rostral muscles, and rostral portions of motor pools innervate rostral fibers within their targets. Here, we implicate A subfamily ephrins in this topographic mapping. First, developing muscles express all five of the ephrin-A genes. Second, rostrally and caudally derived m...

Selective disruption of one Cartesian axis of cortical maps and receptive fields by deficiency in ephrin-As and structur...

Published in Neuron

The topographic representation of visual space is preserved from retina to thalamus to cortex. We have previously shown that precise mapping of thalamocortical projections requires both molecular cues and structured retinal activity. To probe the interaction between these two mechanisms, we studied mice deficient in both ephrin-As and retinal waves...

Ephrin-As mediate targeting of eye-specific projections to the lateral geniculate nucleus.

Published in Nature Neuroscience

Axon guidance cues contributing to the development of eye-specific visual projections to the lateral geniculate nucleus (LGN) have not previously been identified. Here we show that gradients of ephrin-As and their receptors (EphAs) direct retinal ganglion cell (RGC) axons from the two eyes into their stereotyped pattern of layers in the LGN. Overex...

Assembly of yeast Sec proteins involved in translocation into the endoplasmic reticulum into a membrane-bound multisubun...

Published in Nature

Secretory-protein translocation into the endoplasmic reticulum (ER) is thought to be catalysed by integral membrane proteins. Genetic selections uncovered three Saccharomyces cerevisiae genes (SEC61, SEC62 and SEC63), mutations in which block import of precursor proteins into the ER lumen in vivo and in vitro. The DNA sequences of SEC62 and SEC63 p...

Spatial-temporal patterns of retinal waves underlying activity-dependent refinement of retinofugal projections.

Published in Neuron

During development, retinal axons project coarsely within their visual targets before refining to form organized synaptic connections. Spontaneous retinal activity, in the form of acetylcholine-driven retinal waves, is proposed to be necessary for establishing these projection patterns. In particular, both axonal terminations of retinal ganglion ce...

Ephrin-As and patterned retinal activity act together in the development of topographic maps in the primary visual syste...

Published in Journal of Neuroscience

The development of topographic maps in the primary visual system is thought to rely on a combination of EphA/ephrin-A interactions and patterned neural activity. Here, we characterize the retinogeniculate and retinocollicular maps of mice mutant for ephrins-A2, -A3, and -A5 (the three ephrin-As expressed in the mouse visual system), mice mutant for...

Making a visual map: mechanisms and molecules.

Published in Current Opinion in Neurobiology

Visual system development utilizes global and local cues to assemble a topographic map of the visual world, arranging synaptic connections into columns and layers. Recent genetic studies have provided new insights into the mechanisms that underlie these processes. In flies, a precise temporal sequence of neural differentiation provides a global org...

Enhanced plasticity of retinothalamic projections in an ephrin-A2/A5 double mutant.

Published in Journal of Neuroscience

Ascending sensory information reaches primary sensory cortical areas via thalamic relay neurons that are organized into modality-specific compartments or nuclei. Although the sensory relay nuclei of the thalamus show consistent modality-specific segregation of afferents, we now show in a wild-type mouse strain that the visual pathway can be surgica...

Visual map development: bidirectional signaling, bifunctional guidance molecules, and competition.

Published in Cold Spring Harbor Perspectives in Biology

Topographic maps are a two-dimensional representation of one neural structure within another and serve as the main strategy to organize sensory information. The retina s projection via axons of retinal ganglion cells to midbrain visual centers, the optic tectum/superior colliculus, is the leading model to elucidate mechanisms of topographic map for...

Retinal input instructs alignment of visual topographic maps.

Published in Cell

Sensory information is represented in the brain in the form of topographic maps, in which neighboring neurons respond to adjacent external stimuli. In the visual system, the superior colliculus receives topographic projections from the retina and primary visual cortex (V1) that are aligned. Alignment may be achieved through the use of a gradient of...