The Scf/Kit pathway implements self-organized epithelial patterning

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The vestibular system implements a linear-nonlinear transformation in order to encode self-motion

Although it is well established that the neural code representing the world changes at each stage of a sensory pathway, the transformations that mediate these changes are not well understood. Here we show that self-motion (i.e. vestibular) sensory information encoded by VIIIth nerve afferents is integrated nonlinearly by post-synaptic central vestibular neurons. This response nonlinearity was characterized by a strong (～50%) attenuation in neuronal sensitivity to low frequency stimuli when presented concurrently with high frequency stimuli. Using computational methods, we further demonstrate that a static boosting nonlinearity in the input-output relationship of central vestibular neurons accounts for this unexpected result. Specifically, when low and high frequency stimuli are presented concurrently, this boosting nonlinearity causes an intensity-dependent bias in the output firing rate, thereby attenuating neuronal sensitivities. We suggest that nonlinear integration of afferent input extends the coding range of central vestibular neurons and enables them to better extract the high frequency features of self-motion when embedded with low frequency motion during natural movements. These findings challenge the traditional notion that the vestibular system uses a linear rate code to transmit information and have important consequences for understanding how the representation of sensory information changes across sensory pathways.     

The nonlinear pathway of Y ganglion cells in the cat retina

Retinal ganglion cells of the Y type in the cat retina produce two different types of response: linear and nonlinear. The nonlinear responses are generated by a separate and independent nonlinear pathway. The functional connectivity in this pathway is analyzed here by comparing the observed second-order frequency responses of Y cells with predictions of a "sandwich model" in which a static nonlinear stage is sandwiched between two linear filters. The model agrees well with the qualitative and quantitative features of the second-order responses. The prefilter in the model may well be the bipolar cells and the nonlinearity and postfilter in the model are probably associated with amacrine cells.     

The effect of photoreceptor coupling and synapse nonlinearity on signal:noise ratio in early visual processing

Electrical coupling of vertebrate photoreceptors is well known to improve the signal: noise ratio in the photoreceptor layer for large-area stimuli. For example, if N photoreceptors are perfectly coupled to each other, the signal: noise ratio is improved for stimuli illuminating more than a number M = square root of N of the receptors but is made worse for small-area stimuli illuminating less than M of the N receptors. Using the model of Lamb & Simon (J. Physiol., Lond. 263, 257 (1976], which treats the photoreceptor layer as a square array of cells, each coupled through a resistive gap junction to the four cells around it, we show that the signal:noise ratio for small-area stimuli is much greater than would be expected from a model in which receptors are assumed to be perfectly coupled. Contrary to predictions made assuming perfect coupling, receptor coupling should not prevent rods from detecting single photons, but whether the single photon signal can be detected at the bipolar cell level depends on how signals are read out of the receptor layer. The signal:noise ratio in bipolar cells postsynaptic to the photo-receptor layer is determined partly by synaptic convergence and nonlinearity in synaptic transmission from receptors. If the synaptic gain decreases with light-induced receptor hyperpolarization, as is found experimentally, then receptor coupling can improve the postsynaptic signal:noise ratio for stimuli illuminating only one receptor, even though coupling decreases the presynaptic signal:noise ratio for such stimuli. Moreover, increasing the number of coupled receptors projecting to a bipolar cell can improve the signal:noise ratio for localized stimuli if the synapse is sufficiently nonlinear (although, for the degree of nonlinearity seen in lower vertebrates, synaptic convergence makes the ratio worse for the single photon event). The fact that receptor coupling and synaptic convergence can, under some circumstances, improve the signal:noise ratio in bipolar cells suggests a principle of retinal design that may compete with the requirements of high spatial resolution.     

The shikimate pathway regulates programmed cell death

Programmed cell death (PCD) is essential for both plant development and stress responses including immunity. However, how plants control PCD is not well-understood. The shikimate pathway is one of the most important metabolic pathways in plants, but its relationship to PCD is unknown. Here, we show that the shikimate pathway promotes PCD in Arabidopsis. We identify a photoperiod-dependent lesion-mimic mutant named Lesion in short-day (lis), which forms spontaneous lesions in short-day conditions. Map-based cloning and whole-genome resequencing reveal that LIS encodes MEE32, a bifunctional enzyme in the shikimate pathway. Metabolic analysis shows that the level of shikimate is dramatically increased in lis. Through genetic screenings, three suppressors of lis (slis) are identified and the causal genes are cloned. SLISes encode proteins upstream of MEE32 in the shikimate pathway. Furthermore, exogenous shikimate treatment causes PCD. Our study uncovers a link between the shikimate pathway and PCD, and suggests that the accumulation of shikimate is an alternative explanation for the action of glyphosate, the most successful herbicide.     

An aberrant retinal pathway and visual centers in Xenopus tadpoles share a common cell surface molecule, A5 antigen

A monoclonal antibody A5 (MAb-A5), which was raised against Xenopus tadpole tectal cells, recognizes a cell surface-related protein molecule (A5 antigen) expressed on the visual centers of Xenopus tadpoles (S. Takagi, T. Tsuji, T. Amagai, T. Takamatsu, and H. Fujisawa, 1987, Dev. Biol. 122, 90-100). The present immunohistochemistry using MAb-A5 indicated that, in addition to the visual centers, A5 antigen was expressed on the general somatic sensory tract in the medulla and spinal cord of Xenopus tadpoles. As the general somatic sensory tract has been shown to be a pathway for ectopically transplanted retinal axons (M. Constantine-Paton and R. R. Capranica, 1976, J. Comp. Neurol. 170, 17-32; M. J. Katz and R. J. Lasek, 1979, J. Comp. Neurol. 183, 817-832), we examined whether retinal axons transplanted close to the spinal cord or medulla preferentially grow into the A5 antigen-positive general somatic sensory tract. We performed eye transplantation at embryonic stages and detected precise locations and trajectories of transplanted retinal axons within the medulla and spinal cord in tadpoles after filling retinal axons with horseradish peroxidase (HRP). HRP histochemistry in combination with MAb-A5 immunohistochemistry indicated that almost all HRP-filled transplanted retinal axons joined the A5 antigen-positive general somatic sensory tract. These findings suggest the involvement of A5 antigen in specific cell-cell recognition between retinal axons and their targets.     

The hormonal pathway controlling cell death during metamorphosis in a hemimetabolous insect

Metamorphosis in holometabolous insects is mainly based on the destruction of larval tissues. Intensive research in Drosophila melanogaster, a model of holometabolan metamorphosis, has shown that the steroid hormone 20-hydroxyecdysone (20E) signals cell death of larval tissues during metamorphosis. However, D. melanogaster shows a highly derived type of development and the mechanisms regulating apoptosis may not be representative in the insect class context. Unfortunately, no functional studies have been carried out to address whether the mechanisms controlling cell death are present in more basal hemimetabolous species. To address this, we have analyzed the apoptosis of the prothoracic gland of the cockroach Blattella germanica, which undergoes stage-specific degeneration just after the imaginal molt. Here, we first show that B. germanica has two inhibitor of apoptosis (IAP) proteins and that one of them, BgIAP1, is continuously required to ensure tissue viability, including that of the prothoracic gland, during nymphal development. Moreover, we demonstrate that the degeneration of the prothoracic gland is controlled by a complex 20E-triggered hierarchy of nuclear receptors converging in the strong activation of the death-inducer Fushi tarazu-factor 1 (BgFTZ-F1) during the nymphal-adult transition. Finally, we have also shown that prothoracic gland degeneration is effectively prevented by the presence of juvenile hormone (JH). Given the relevance of cell death in the metamorphic process, the characterization of the molecular mechanisms regulating apoptosis in hemimetabolous insects would allow to help elucidate how metamorphosis has evolved from less to more derived insect species.     

Neuropeptide Y in the recurrent mossy fiber pathway

In the epileptic brain, hippocampal dentate granule cells become synaptically interconnected through the sprouting of mossy fibers. This new circuitry is expected to facilitate epileptiform discharge. Prolonged seizures induce the long-lasting neoexpression of neuropeptide Y (NPY) in mossy fibers. NPY is released spontaneously from recurrent mossy fiber terminals, reduces glutamate release from those terminals by activating presynaptic Y2 receptors, and depresses granule cell epileptiform activity dependent on the recurrent pathway. These effects are much greater in rats than in C57BL/6 mice, despite apparently equivalent mossy fiber sprouting and neoexpression of NPY. This species difference can be explained by contrasting changes in the expression of mossy fiber Y2 receptors; seizures upregulate Y2 receptors in rats but downregulate them in mice. The recurrent mossy fiber pathway may synchronize granule cell discharge more effectively in humans and mice than in rats, due to its lower expression of either NPY (humans) or Y2 receptors (mice).     

The N-acylation-phosphodiesterase pathway and cell signalling

Long-chain N-acylethanolamines (NAEs) elicit a variety of biological and pharmacological effects, Anandamide (20:4n-6 NAE) and other polyunsaturated NAEs bind to the cannabinoid receptor and may thus serve as highly specific lipid mediators of cell signalling. NAEs can be formed by phospholipase D-catalyzed hydrolysis of N-acylethanolamine phospholipids or by direct condensation of ethanolamine and fatty acid, So far, most of the latter biosynthetic activity has been shown to be the reverse reaction of the NAE amidohydrolase that catalyzes NAE degradation. Thus, increasing evidence supports the hypothesis that the N-acylation-phosphodiesterase pathway yields not only saturated-monounsaturated NAEs, but polyunsaturated ones, including anandamide, as well.     

Profound contrast adaptation early in the visual pathway

Prior exposure to a moving grating of high contrast led to a substantial and persistent reduction in the contrast sensitivity of neurons in the lateral geniculate nucleus (LGN) of macaque. This slow contrast adaptation was potent in all magnocellular (M) cells but essentially absent in parvocellular (P) cells and neurons that received input from S cones. Simultaneous recordings of M cells and the potentials of ganglion cells driving them showed that adaptation originated in ganglion cells. As expected from the spatiotemporal tuning of M cells, adaptation was broadly tuned for spatial frequency and lacked orientation selectivity. Adaptation could be induced by high temporal frequencies to which cortical neurons do not respond, but not by low temporal frequencies that can strongly adapt cortical neurons. Our observations confirm that contrast adaptation occurs at multiple levels in the visual system, and they provide a new way to reveal the function and perceptual significance of the M pathway.     

The endoplasmic reticulum is a key component of the plasma cell death pathway

Plasma cells (PC) are the effector cells of the humoral Ab response. Unlike other dedicated secretory cells, they exist as two populations with opposite cell fates: short-lived and long-lived PC. Upon transformation they lead to an incurable neoplasia called multiple myeloma. In this study we have explored the molecular mechanism of PC death. Our data show that their apoptotic pathway is unique among other hemopoietic cells inasmuch as neither the death receptors nor the mitochondria play the central role. PC apoptosis is initiated by activation of Bax at the endoplasmic reticulum membrane and subsequent activation of the endoplasmic reticulum-associated caspase-4 before the release of mitochondrial apoptogenic factors. Together, our observations indicate that the cardinal function of PC (i.e., Ig secretion) is also the cause of their death.