Brain Structure and Function

, Volume 223, Issue 3, pp 1107–1120 | Cite as

Morphological determinants of dendritic arborization neurons in Drosophila larva

  • Sumit Nanda
  • Ravi Das
  • Shatabdi Bhattacharjee
  • Daniel N. Cox
  • Giorgio A. Ascoli
Original Article

Abstract

Pairing in vivo imaging and computational modeling of dendritic arborization (da) neurons from the fruit fly larva provides a unique window into neuronal growth and underlying molecular processes. We image, reconstruct, and analyze the morphology of wild-type, RNAi-silenced, and mutant da neurons. We then use local and global rule-based stochastic simulations to generate artificial arbors, and identify the parameters that statistically best approximate the real data. We observe structural homeostasis in all da classes, where an increase in size of one dendritic stem is compensated by a reduction in the other stems of the same neuron. Local rule models show that bifurcation probability is determined by branch order, while branch length depends on path distance from the soma. Global rule simulations suggest that most complex morphologies tend to be constrained by resource optimization, while simpler neuron classes privilege path distance conservation. Genetic manipulations affect both the local and global optimal parameters, demonstrating functional perturbations in growth mechanisms.

Keywords

Neuronal development Molecular neurogenetics Confocal microscopy Morphological reconstructions Computational modeling 

Notes

Acknowledgements

The authors sincerely thank Cox Lab members Sarah G. Clark and Atit A. Patel for the image stack generation; and Ascoli Lab members Griffin Badalamente, Alisha Compton, Anna Lulushi and Margaret Kirtley for help with neuronal reconstructions; Rubén Armañanzas for ideas and brain storming; and Diek Wheeler for critical review of the manuscript. Supported by National institute of Health: NIH NS39600, NIH NS086082, NIH MH086928 and National Science Foundation: NSF DBI1546335 and NSF BCS1663755. Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study.

Supplementary material

429_2017_1541_MOESM1_ESM.pptx (1.7 mb)
Supplementary material 1 (PPTX 1699 kb)

References

  1. Ascoli GA (2002) Neuroanatomical algorithms for dendritic modeling. Network 13:247–260.  https://doi.org/10.1088/0954-898X/13/3/301 CrossRefPubMedGoogle Scholar
  2. Ascoli GA, Krichmar JL (2000) l-Neuron: a modeling tool for the efficient generation and parsimonious description of dendritic morphology. Neurocomputing 32–33:1003–1011.  https://doi.org/10.1016/S0925-2312(00)00272-1 CrossRefGoogle Scholar
  3. Ascoli GA, Donohue DE, Halavi M (2007) NeuroMorpho.Org: a central resource for neuronal morphologies. J Neurosci 27:9247–9251.  https://doi.org/10.1523/JNEUROSCI.2055-07.2007 CrossRefPubMedGoogle Scholar
  4. Bird AD, Cuntz H (2016) Optimal current transfer in dendrites. PLoS Comput Biol 12:e1004897.  https://doi.org/10.1371/journal.pcbi.1004897 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Brill MS, Kleele T, Ruschkies L et al (2016) Branch-specific microtubule destabilization mediates axon branch loss during neuromuscular synapse elimination. Neuron 92:845–856.  https://doi.org/10.1016/j.neuron.2016.09.049 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Burke RE, Marks WB, Ulfhake B (1992) A parsimonious description of motoneuron dendritic morphology using computer simulation. J Neurosci 12:2403–2416PubMedGoogle Scholar
  7. Corty MM, Matthews BJ, Grueber WB (2009) Molecules and mechanisms of dendrite development in Drosophila. Development 136:1049–1061.  https://doi.org/10.1242/dev.014423 CrossRefPubMedPubMedCentralGoogle Scholar
  8. Couton L, Mauss AS, Yunusov T et al (2015) Development of connectivity in a motoneuronal network in Drosophila larvae. Curr Biol 25:568–576.  https://doi.org/10.1016/j.cub.2014.12.056 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Cuntz H, Forstner F, Borst A, Häusser M (2010) One rule to grow them all: a general theory of neuronal branching and its practical application. PLoS Comput Biol 6(8):e1000877.  https://doi.org/10.1371/journal.pcbi.1000877 CrossRefPubMedPubMedCentralGoogle Scholar
  10. Donohue DE, Ascoli GA (2005) Models of neuronal outgrowth. In: Koslow SH, Subramaniam S (eds) Databasing the brain: from data to knowledge. Wiley Press, Hobokenm, pp 303–323Google Scholar
  11. Donohue DE, Ascoli GA (2008) A comparative computer simulation of dendritic morphology. PLoS Comput Biol 4(5):e1000089.  https://doi.org/10.1371/journal.pcbi.1000089 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Feng L, Zhao T, Kim J (2015) neuTube 1.0: a new design for efficient neuron reconstruction software based on the SWC Format. eNeuro.  https://doi.org/10.1523/ENEURO.0049-14.2014 PubMedCentralGoogle Scholar
  13. Gao FB (2007) Molecular and cellular mechanisms of dendritic morphogenesis. Curr Opin Neurobiol 17:525–532.  https://doi.org/10.1016/j.conb.2007.08.004 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Grueber WB, Jan LY, Jan YN (2002) Tiling of the Drosophila epidermis by multidendritic sensory neurons. Development 129:2867–2878.  https://doi.org/10.1083/jcb.140.1.143 PubMedGoogle Scholar
  15. Grueber WB, Jan LY, Jan YN (2003) Different levels of the homeodomain protein cut regulate distinct dendrite branching patterns of Drosophila multidendritic neurons. Cell 112:805–818.  https://doi.org/10.1016/S0092-8674(03)00160-0 CrossRefPubMedGoogle Scholar
  16. Hillman D (1979) Neuronal shape parameters and substructures as a basis of neuronal form. In: Schmitt F (ed) The Neurosciences, 4th Study. MIT Press, Cambridge, pp 477–498Google Scholar
  17. Iyer EPR, Iyer SC, Sullivan L et al (2013) Functional genomic analyses of two morphologically distinct classes of Drosophila sensory neurons: post-mitotic roles of transcription factors in dendritic patterning. PLoS One 8(8):e72434.  https://doi.org/10.1371/journal.pone.0072434 CrossRefPubMedPubMedCentralGoogle Scholar
  18. Jan YN, Jan LY (2010) Branching out: mechanisms of dendritic arborization. Nat Rev Neurosci 11:316–328.  https://doi.org/10.1038/nrn2854 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Jinushi-Nakao S, Arvind R, Amikura R et al (2007) Knot/collier and cut control different aspects of dendrite cytoskeleton and synergize to define final arbor shape. Neuron 56(6):963–978.  https://doi.org/10.1016/j.neuron.2007.10.031 CrossRefPubMedGoogle Scholar
  20. Koene RA, Tijms B, Van Hees P et al (2009) NETMORPH: a framework for the stochastic generation of large scale neuronal networks with realistic neuron morphologies. Neuroinformatics 7:195–210.  https://doi.org/10.1007/s12021-009-9052-3 CrossRefPubMedGoogle Scholar
  21. Kole MHP, Czeh B, Fuchs E (2004) Homeostatic maintenance in excitability of tree shrew hippocampal CA3 pyramidal neurons after chronic stress. Hippocampus 14:742–751.  https://doi.org/10.1002/hipo.10212 CrossRefPubMedGoogle Scholar
  22. London M, Häusser M (2005) Dendritic computation. Annu Rev Neurosci 28:503–532.  https://doi.org/10.1146/annurev.neuro.28.061604.135703 CrossRefPubMedGoogle Scholar
  23. Mainen ZF, Sejnowski TJ (1996) Influence of dendritic structure on firing pattern in model neocortical neurons. Nature 382:363–366.  https://doi.org/10.1038/382363a0 CrossRefPubMedGoogle Scholar
  24. Nguyen MD, Shu T, Sanada K et al (2004) A NUDEL-dependent mechanism of neurofilament assembly regulates the integrity of CNS neurons. Nat Cell Biol 6:595–608.  https://doi.org/10.1038/ncb1139 CrossRefPubMedGoogle Scholar
  25. Parrish JZ, Emoto K, Kim MD, Jan YN (2007) Mechanisms that regulate establishment, maintenance, and remodeling of dendritic fields. Annu Rev Neurosci 30:399–423.  https://doi.org/10.1146/annurev.neuro.29.051605.112907 CrossRefPubMedGoogle Scholar
  26. Peng H, Bria A, Zhou Z et al (2014) Extensible visualization and analysis for multidimensional images using Vaa3D. Nat Protoc 9:193–208.  https://doi.org/10.1038/nprot.2014.011 CrossRefPubMedGoogle Scholar
  27. Ramón y Cajal S (1995) Histology of the nervous system of man and vertebrates. Oxford University Press, New YorkGoogle Scholar
  28. Samsonovich AV, Ascoli GA (2005) Statistical determinants of dendritic morphology in hippocampal pyramidal neurons: a hidden Markov model. Hippocampus 15:166–183.  https://doi.org/10.1002/hipo.20041 CrossRefPubMedGoogle Scholar
  29. Samsonovich AV, Ascoli GA (2006) Morphological homeostasis in cortical dendrites. Proc Natl Acad Sci USA 103:1569–1574.  https://doi.org/10.1073/pnas.0510057103 CrossRefPubMedPubMedCentralGoogle Scholar
  30. Scorcioni R, Polavaram S, Ascoli GA (2008) L-Measure: a web-accessible tool for the analysis, comparison and search of digital reconstructions of neuronal morphologies. Nat Protoc 3:866–876.  https://doi.org/10.1038/nprot.2008.51 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Singhania A, Grueber WB (2014) Development of the embryonic and larval peripheral nervous system of Drosophila. Wiley Interdiscip Rev Dev Biol 3:193–210.  https://doi.org/10.1002/wdev.135 CrossRefPubMedPubMedCentralGoogle Scholar
  32. Strahler AN (1953) Revisions of Horton’s quantitative factors in erosional terrain. Trans Am Geophys Union 34:345Google Scholar
  33. Sulkowski MJ, Iyer SC, Kurosawa MS et al (2011) Turtle functions downstream of cut in differentially regulating class specific dendrite morphogenesis in Drosophila. PLoS One 6:e22611.  https://doi.org/10.1371/journal.pone.0022611 CrossRefPubMedPubMedCentralGoogle Scholar
  34. Tavosanis G (2014) The Cell Biology of Dendrite Differentiation. In: Cuntz H, Remme MWH, Torben-Nielsen B (eds) The computing dendrite: from structure to function. Springer, New York, pp 23–40CrossRefGoogle Scholar
  35. Tripodi M, Evers JF, Mauss A, Bate M, Landgraf M (2008) Structural homeostasis: compensatory adjustments of dendritic arbor geometry in response to variations of synaptic input. PLoS Biol 6(10):e260.  https://doi.org/10.1371/journal.pbio.0060260 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Turner HN, Armengol K, Patel AA et al (2016) The TRP channels Pkd2, NompC, and Trpm act in cold-sensing neurons to mediate unique aversive behaviors to noxious cold in Drosophila. Curr Biol 26(23):3116–3128.  https://doi.org/10.1016/j.cub.2016.09.038 CrossRefPubMedPubMedCentralGoogle Scholar
  37. Turrigiano GG, Nelson SB (2004) Homeostatic plasticity in the developing nervous system. Nat Rev Neurosci 5:97–107.  https://doi.org/10.1038/nrn1327 CrossRefPubMedGoogle Scholar
  38. Uemura E, Carriquiry A, Kliemann W, Goodwin J (1995) Mathematical modeling of dendritic growth in vitro. Brain Res 671:187–194.  https://doi.org/10.1016/0006-8993(94)01310-E CrossRefPubMedGoogle Scholar
  39. Uylings HBM, Smit GJ, Veltman WAM (1975) Ordering methods in quantitative analysis of branching structures of dendritic trees. Adv Neurol 12:247–254Google Scholar
  40. van Beuningen SF, Hoogenraad CC (2016) Neuronal polarity: remodeling microtubule organization. Curr Opin Neurobiol 39:1–7.  https://doi.org/10.1016/j.conb.2016.02.003 CrossRefPubMedGoogle Scholar
  41. van Beuningen SFB, Will L, Harterink M et al (2015) TRIM46 controls neuronal polarity and axon specification by driving the formation of parallel microtubule arrays. Neuron 88:1208–1226.  https://doi.org/10.1016/j.neuron.2015.11.012 CrossRefPubMedGoogle Scholar
  42. van Pelt J, Schierwagen A (2004) Morphological analysis and modeling of neuronal dendrites. Math Biosci 188:147–155.  https://doi.org/10.1016/j.mbs.2003.08.006 CrossRefPubMedGoogle Scholar
  43. van Pelt J, Uylings HBM (2002) Branching rates and growth functions in the outgrowth of dendritic branching patterns. Network 13:261–281CrossRefPubMedGoogle Scholar
  44. van Pelt J, Dityatev AE, Uylings HB (1997) Natural variability in the number of dendritic segments: model-based inferences about branching during neurite outgrowth. J Comp Neurol 387(3):325–340.  https://doi.org/10.1002/(SICI)1096-9861(19971027)387:3<325:AID-CNE1>3.0.CO;2-2 CrossRefPubMedGoogle Scholar
  45. Vetter P, Roth A, Häusser M (2001) Propagation of action potentials in dendrites depends on dendritic morphology. J Neurophysiol 85:926–937CrossRefPubMedGoogle Scholar
  46. Wang X, Kim JH, Bazzi M et al (2013) Bimodal control of dendritic and axonal growth by the Dual Leucine Zipper Kinase Pathway. PLoS Biol.  https://doi.org/10.1371/journal.pbio.1001572 Google Scholar
  47. Welch ABL (1947) The generalization of ‘Student’s’ problem when several different population variances are involved. Biometrika 34:28–35. Stable url: http://www.jstor.org/stable/2332510
  48. Wong JJ, Li S, Lim EK et al (2013) A Cullin1-based SCF E3 Ubiquitin Ligase targets the InR/PI3K/TOR pathway to regulate neuronal pruning. PLoS Biol 11(9):e1001657.  https://doi.org/10.1371/journal.pbio.1001657 CrossRefPubMedPubMedCentralGoogle Scholar
  49. Xiang Y, Yuan Q, Vogt N et al (2010) Light-avoidance-mediating photoreceptors tile the Drosophila larval body wall. Nature 468:921–926.  https://doi.org/10.1038/nature09576 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Sumit Nanda
    • 1
  • Ravi Das
    • 2
  • Shatabdi Bhattacharjee
    • 2
  • Daniel N. Cox
    • 2
  • Giorgio A. Ascoli
    • 1
  1. 1.Center for Neural Informatics, Structures, and Plasticity, Krasnow Institute for Advanced StudyGeorge Mason UniversityFairfaxUSA
  2. 2.Neuroscience InstituteGeorgia State UniversityAtlantaUSA

Personalised recommendations