Brain asymmetry is encoded at the level of axon terminal morphology

Neural Development - 2008
Isaac H. Bianco1, Michael Carl1, Claire Russell1, Jonathan D.W. Clarke1, Stephen W. Wilson1
1Department of Cell and Developmental Biology, UCL, Gower St, London WC1E 6BT, UK

Tóm tắt

Abstract Background Functional lateralization is a conserved feature of the central nervous system (CNS). However, underlying left-right asymmetries within neural circuitry and the mechanisms by which they develop are poorly described. Results In this study, we use focal electroporation to examine the morphology and connectivity of individual neurons of the lateralized habenular nuclei. Habenular projection neurons on both sides of the brain share a stereotypical unipolar morphology and elaborate remarkable spiraling terminal arbors in their target interpeduncular nucleus, a morphology unlike that of any other class of neuron described to date. There are two quite distinct sub-types of axon arbor that differ both in branching morphology and in their localization within the target nucleus. Critically, both arbor morphologies are elaborated by both left and right-sided neurons, but at greatly differing frequencies. We show that these differences in cell type composition account for the gross connectional asymmetry displayed by the left and right habenulae. Analysis of the morphology and projections of individual post-synaptic neurons suggests that the target nucleus has the capacity to either integrate left and right inputs or to handle them independently, potentially relaying information from the left and right habenulae within distinct downstream pathways, thus preserving left-right coding. Furthermore, we find that signaling from the unilateral, left-sided parapineal nucleus is necessary for both left and right axons to develop arbors with appropriate morphology and targeting. However, following parapineal ablation, left and right habenular neurons continue to elaborate arbors with distinct, lateralized morphologies. Conclusion By taking the analysis of asymmetric neural circuitry to the level of single cells, we have resolved left-right differences in circuit microarchitecture and show that lateralization can be recognized at the level of the morphology and connectivity of single projection neuron axons. Crucially, the same circuitry components are specified on both sides of the brain, but differences in the ratios of different neuronal sub-types results in a lateralized neural architecture and gross connectional asymmetry. Although signaling from the parapineal is essential for the development of normal lateralization, additional factors clearly act during development to confer left-right identity upon neurons in this highly conserved circuit.

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Tài liệu tham khảo

Rogers LJ, Andrew RJ: Comparitive Vertebrate Lateralization. 2002, Cambridge, Cambridge University Press

Pascual A, Huang KL, Neveu J, Preat T: Neuroanatomy: brain asymmetry and long-term memory. Nature. 2004, 427: 605-606. 10.1038/427605a.

Chuang CF, Vanhoven MK, Fetter RD, Verselis VK, Bargmann CI: An innexin-dependent cell network establishes left-right neuronal asymmetry in C. elegans. Cell. 2007, 129: 787-799. 10.1016/j.cell.2007.02.052.

Vallortigara G, Rogers LJ: Survival with an asymmetrical brain: advantages and disadvantages of cerebral lateralization. Behav Brain Sci. 2005, 28: 575-89; discussion 589-633. 10.1017/S0140525X05000105.

Toga AW, Thompson PM: Mapping brain asymmetry. Nat Rev Neurosci. 2003, 4: 37-48. 10.1038/nrn1009.

Halpern ME, Gunturkun O, Hopkins WD, Rogers LJ: Lateralization of the vertebrate brain: taking the side of model systems. J Neurosci. 2005, 25: 10351-10357. 10.1523/JNEUROSCI.3439-05.2005.

Anderson B, Southern BD, Powers RE: Anatomic asymmetries of the posterior superior temporal lobes: a postmortem study. Neuropsychiatry Neuropsychol Behav Neurol. 1999, 12: 247-254.

Kawakami R, Shinohara Y, Kato Y, Sugiyama H, Shigemoto R, Ito I: Asymmetrical allocation of NMDA receptor epsilon2 subunits in hippocampal circuitry. Science. 2003, 300: 990-994. 10.1126/science.1082609.

Concha ML: The dorsal diencephalic conduction system of zebrafish as a model of vertebrate brain lateralisation. Neuroreport. 2004, 15: 1843-1846. 10.1097/00001756-200408260-00001.

Sutherland RJ: The dorsal diencephalic conduction system: a review of the anatomy and functions of the habenular complex. Neurosci Biobehav Rev. 1982, 6: 1-13. 10.1016/0149-7634(82)90003-3.

Concha ML, Wilson SW: Asymmetry in the epithalamus of vertebrates. J Anat. 2001, 199: 63-84. 10.1017/S0021878201008329.

Concha ML, Russell C, Regan JC, Tawk M, Sidi S, Gilmour DT, Kapsimali M, Sumoy L, Goldstone K, Amaya E, Kimelman D, Nicolson T, Grunder S, Gomperts M, Clarke JD, Wilson SW: Local tissue interactions across the dorsal midline of the forebrain establish CNS laterality. Neuron. 2003, 39: 423-438. 10.1016/S0896-6273(03)00437-9.

Concha ML, Burdine RD, Russell C, Schier AF, Wilson SW: A nodal signaling pathway regulates the laterality of neuroanatomical asymmetries in the zebrafish forebrain. Neuron. 2000, 28: 399-409. 10.1016/S0896-6273(00)00120-3.

Gamse JT, Thisse C, Thisse B, Halpern ME: The parapineal mediates left-right asymmetry in the zebrafish diencephalon. Development. 2003, 130: 1059-1068. 10.1242/dev.00270.

Gamse JT, Kuan YS, Macurak M, Brosamle C, Thisse B, Thisse C, Halpern ME: Directional asymmetry of the zebrafish epithalamus guides dorsoventral innervation of the midbrain target. Development. 2005, 132: 4869-4881. 10.1242/dev.02046.

Aizawa H, Bianco IH, Hamaoka T, Miyashita T, Uemura O, Concha ML, Russell C, Wilson SW, Okamoto H: Laterotopic Representation of Left-Right Information onto the Dorso-Ventral Axis of a Zebrafish Midbrain Target Nucleus. Curr Biol. 2005, 15: 238-243. 10.1016/j.cub.2005.01.014.

Meyer MP, Smith SJ: Evidence from in vivo imaging that synaptogenesis guides the growth and branching of axonal arbors by two distinct mechanisms. J Neurosci. 2006, 26: 3604-3614. 10.1523/JNEUROSCI.0223-06.2006.

Morley BJ: The interpeduncular nucleus. Int Rev Neurobiol. 1986, 28: 157-182.

Kuan YS, Yu HH, Moens CB, Halpern ME: Neuropilin asymmetry mediates a left-right difference in habenular connectivity. Development. 2007

Hendricks M, Jesuthasan S: Asymmetric innervation of the habenula in zebrafish. J Comp Neurol. 2007, 502: 611-619. 10.1002/cne.21339.

Herrick CJ: The Brain of the Tiger Salamander. 1948, , The University of Chicago Press

Cajal SR: Histology of the Nervous System of Man and Vertebrates. 1995, , Oxford University Press

Fraley SM, Sharma SC: Topography of retinal axons in the diencephalon of goldfish. Cell Tissue Res. 1984, 238: 529-538. 10.1007/BF00219869.

Kaprielian Z, Runko E, Imondi R: Axon guidance at the midline choice point. Dev Dyn. 2001, 221: 154-181. 10.1002/dvdy.1143.

Kidd T, Brose K, Mitchell KJ, Fetter RD, Tessier-Lavigne M, Goodman CS, Tear G: Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors. Cell. 1998, 92: 205-215. 10.1016/S0092-8674(00)80915-0.

Seeger M, Tear G, Ferres-Marco D, Goodman CS: Mutations affecting growth cone guidance in Drosophila: genes necessary for guidance toward or away from the midline. Neuron. 1993, 10: 409-426. 10.1016/0896-6273(93)90330-T.

Aizawa H, Goto M, Sato T, Okamoto H: Temporally regulated asymmetric neurogenesis causes left-right difference in the zebrafish habenular structures. Dev Cell. 2007, 12: 87-98. 10.1016/j.devcel.2006.10.004.

Lenn NJ: Synapses in the interpeduncular nucleus: electron microscopy of normal and habenula lesioned rats. J Comp Neurol. 1976, 166: 77-99. 10.1002/cne.901660106.

Lenn NJ, Wong V, Hamill GS: Left-right pairing at the crest synapses of rat interpeduncular nucleus. Neuroscience. 1983, 9: 383-389. 10.1016/0306-4522(83)90301-9.

Gilmour DT, Maischein HM, Nusslein-Volhard C: Migration and function of a glial subtype in the vertebrate peripheral nervous system. Neuron. 2002, 34: 577-588. 10.1016/S0896-6273(02)00683-9.

Pauls S, Geldmacher-Voss B, Campos-Ortega JA: A zebrafish histone variant H2A.F/Z and a transgenic H2A.F/Z:GFP fusion protein for in vivo studies of embryonic development. Dev Genes Evol. 2001, 211: 603-610. 10.1007/s00427-001-0196-x.

Choo BG, Kondrichin I, Parinov S, Emelyanov A, Go W, Toh WC, Korzh V: Zebrafish transgenic Enhancer TRAP line database (ZETRAP). BMC Dev Biol. 2006, 6: 5-10.1186/1471-213X-6-5.

Parinov S, Kondrichin I, Korzh V, Emelyanov A: Tol2 transposon-mediated enhancer trap to identify developmentally regulated zebrafish genes in vivo. Dev Dyn. 2004, 231: 449-459. 10.1002/dvdy.20157.

Westerfield M: The zebrafish book. 1995, , Eugene, OR: University of Oregon

Haas K, Sin WC, Javaherian A, Li Z, Cline HT: Single-cell electroporation for gene transfer in vivo. Neuron. 2001, 29: 583-591. 10.1016/S0896-6273(01)00235-5.

Shanmugalingam S, Houart C, Picker A, Reifers F, Macdonald R, Barth A, Griffin K, Brand M, Wilson SW: Ace/Fgf8 is required for forebrain commissure formation and patterning of the telencephalon. Development. 2000, 127: 2549-2561.

Motulsky HJ, Christopoulos A: Fitting models to biological data using linear and nonlinear regression. A practical guide to curve fitting. 2003, San Diego CA, GraphPad Software Inc.

Burnham KP, Anderson DR: Model Selection and Multimodel Inference - A practical Information-theoretic approach. 2002, , Springer, 2nd

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