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Articles by Joshua T. Gamse in JoVE
Other articles by Joshua T. Gamse on PubMed
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Directional Asymmetry of the Zebrafish Epithalamus Guides Dorsoventral Innervation of the Midbrain Target
Development (Cambridge, England).
Nov, 2005 |
Pubmed ID: 16207761 The zebrafish epithalamus, consisting of the pineal complex and flanking dorsal habenular nuclei, provides a valuable model for exploring how left-right differences could arise in the vertebrate brain. The parapineal lies to the left of the pineal and the left habenula is larger, has expanded dense neuropil, and distinct patterns of gene expression from the right habenula. Under the influence of Nodal signaling, positioning of the parapineal sets the direction of habenular asymmetry and thereby determines the left-right origin of habenular projections onto the midbrain target, the interpeduncular nucleus (IPN). In zebrafish with parapineal reversal, neurons from the left habenula project to a more limited ventral IPN region where right habenular axons would normally project. Conversely, efferents from the right habenula adopt a more extensive dorsoventral IPN projection pattern typical of left habenular neurons. Three members of the leftover-related KCTD (potassium channel tetramerization domain containing) gene family are expressed differently by the left and right habenula, in patterns that define asymmetric subnuclei. Molecular asymmetry extends to protein levels in habenular efferents, providing additional evidence that left and right axons terminate within different dorsoventral regions of the midbrain target. Laser-mediated ablation of the parapineal disrupts habenular asymmetry and consequently alters the dorsoventral distribution of innervating axons. The results demonstrate that laterality of the dorsal forebrain influences the formation of midbrain connections and their molecular properties.
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Knockdown of Nav1.6a Na+ Channels Affects Zebrafish Motoneuron Development
Development (Cambridge, England).
Oct, 2006 |
Pubmed ID: 16943272 In addition to rapid signaling, electrical activity provides important cues to developing neurons. Electrical activity relies on the function of several different types of voltage-gated ion channels. Whereas voltage-gated Ca2+ channel activity regulates several aspects of neuronal differentiation, much less is known about developmental roles of voltage-gated Na+ channels, essential mediators of electrical signaling. Here, we focus on the zebrafish Na+ channel isotype, Nav1.6a, which is encoded by the scn8a gene. A restricted set of spinal neurons, including dorsal sensory Rohon-Beard cells, two motoneuron subtypes with different axonal trajectories, express scn8a during embryonic development. CaP, an early born primary motoneuron subtype with ventrally projecting axons expresses scn8a, as does a class of secondary motoneurons with axons that project dorsally. To test for developmental roles of scn8a, we knocked down Nav1.6a protein using antisense morpholinos. Na+ channel protein and current amplitudes were reduced in neurons that express scn8a. Furthermore, Nav1.6a knockdown altered axonal morphologies of some but not all motoneurons. Dorsally projecting secondary motoneurons express scn8a and displayed delayed axonal outgrowth. By contrast, CaP axons developed normally, despite expression of the gene. Surprisingly, ventrally projecting secondary motoneurons, a population in which scn8a was not detected, displayed aberrant axonal morphologies. Mosaic analysis indicated that effects on ventrally projecting secondary motoneurons were non cell-autonomous. Thus, voltage-gated Na+ channels play cell-autonomous and non cell-autonomous roles during neuronal development.
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Selective Asymmetry in a Conserved Forebrain to Midbrain Projection
Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution.
Sep, 2007 |
Pubmed ID: 17592620 How the left and right sides of the brain acquire anatomical and functional specializations is not well understood. The zebrafish has proven to be a useful model to explore the genetic basis of neuroanatomical asymmetry in the developing forebrain. The dorsal diencephalon or epithalamus consists of the asymmetric pineal complex and adjacent paired nuclei, the left and right medial habenulae, which in zebrafish larvae, exhibit differences in their size, neuropil density and patterns of gene expression. In all vertebrates, axons from the medial habenular nuclei project within a prominent fiber bundle, the fasciculus retroflexus, to a shared midbrain target, the interpeduncular nucleus of the ventral tegmentum. However, in zebrafish, projections from the left habenula innervate the dorsal and ventral regions of the target nucleus, whereas right habenular efferents project only to the ventral region. A similar dorsoventral difference in habenular connectivity is found in another teleost species, the highly derived southern flounder, Paralichthys lethostima. In this flatfish, directional asymmetry of the habenular projection appears to be independent of the left-right morphology and orientation that an individual adopts post-metamorphosis. Comparative anterograde labeling of the brains of salamanders, frogs and mice reveals that axons emanating from the left and right medial habenulae do not project to different domains, but rather, they traverse the target nucleus in a complementary mirror image pattern. Thus, although the habenulo-interpeduncular conduction system is highly conserved in the vertebrate brain, the stereotypic dorsoventral topography of left-right connections appears to be a feature that is specific to teleosts.
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Tbx2b is Required for Ultraviolet Photoreceptor Cell Specification During Zebrafish Retinal Development
Proceedings of the National Academy of Sciences of the United States of America.
Feb, 2009 |
Pubmed ID: 19179291 The vertebrate rod and cone photoreceptors are highly specialized sensory neurons that transduce light into the chemical and electrical signals of the nervous system. Although the physiological properties of cones and rods are well known, only a handful of genes have been identified that regulate the specification of photoreceptor subtypes. Taking advantage of the mosaic organization of photoreceptors in zebrafish, we report the isolation of a mutation resulting in a unique change in photoreceptor cell fate. Mutation of the lots-of-rods (lor) locus results in a near one-for-one transformation of UV-cone precursors into rods. The transformed cells exhibit morphological characteristics and a gene-expression pattern typical of rods, but differentiate in a temporal and spatial pattern consistent with UV-cone development. In mutant larvae and adults, the highly ordered photoreceptor mosaic is maintained and degeneration is not observed, suggesting that lor functions after the specification of the other photoreceptor subtypes. In genetic chimeras, lor functions cell-autonomously in the specification of photoreceptor cell fate. Linkage analysis and genetic-complementation testing indicate that lor is an allele of tbx2b/fby (from beyond). fby was identified by a pineal complex phenotype, and carries a nonsense mutation in the T-box domain of the tbx2b transcription factor. Homozygous fby mutant larvae and lor/fby transheterozygotes also display the lots-of-rods phenotype. Based upon these data, we propose a previously undescribed function for tbx2b in photoreceptor cell precursors, to promote the UV cone fate by repressing the rod differentiation pathway.
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Subnuclear Development of the Zebrafish Habenular Nuclei Requires ER Translocon Function
Developmental Biology.
Dec, 2011 |
Pubmed ID: 21945073 The dorsal habenular nuclei (Dh) of the zebrafish are characterized by significant left-right differences in gene expression, anatomy, and connectivity. Notably, the lateral subnucleus of the Dh (LsDh) is larger on the left side of the brain than on the right, while the medial subnucleus (MsDh) is larger on the right compared to the left. A screen for mutations that affect habenular laterality led to the identification of the sec61a-like 1(sec61al1) gene. In sec61al1(c163) mutants, more neurons in the LsDh and fewer in the MsDh develop on both sides of the brain. Generation of neurons in the LsDh occurs more rapidly and continues for a longer time period in mutants than in WT. Expression of Nodal pathway genes on the left side of the embryos is unaffected in mutants, as is the left sided placement of the parapineal organ, which promotes neurogenesis in the LsDh of WT embryos. Ultrastructural analysis of the epithalamus indicates that ventricular precursor cells, which form an epithelium in WT embryos, lose apical-basal polarity in sec61al1(c163) mutants. Our results show that in the absence of sec61al1, an excess of precursor cells for the LsDh exit the ventricular region and differentiate, resulting in formation of bilaterally symmetric habenular nuclei.
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