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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ascoli GA (2002) Neuroanatomical algorithms for dendritic modeling. Network 13:247–260. https://doi.org/10.1088/0954-898X/13/3/301
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
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
Bird AD, Cuntz H (2016) Optimal current transfer in dendrites. PLoS Comput Biol 12:e1004897. https://doi.org/10.1371/journal.pcbi.1004897
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
Burke RE, Marks WB, Ulfhake B (1992) A parsimonious description of motoneuron dendritic morphology using computer simulation. J Neurosci 12:2403–2416
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
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
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
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 303–323
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
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
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
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
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
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 477–498
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
Jan YN, Jan LY (2010) Branching out: mechanisms of dendritic arborization. Nat Rev Neurosci 11:316–328. https://doi.org/10.1038/nrn2854
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
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
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
London M, Häusser M (2005) Dendritic computation. Annu Rev Neurosci 28:503–532. https://doi.org/10.1146/annurev.neuro.28.061604.135703
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
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
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
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
Ramón y Cajal S (1995) Histology of the nervous system of man and vertebrates. Oxford University Press, New York
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
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
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
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
Strahler AN (1953) Revisions of Horton’s quantitative factors in erosional terrain. Trans Am Geophys Union 34:345
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
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 23–40
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
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
Turrigiano GG, Nelson SB (2004) Homeostatic plasticity in the developing nervous system. Nat Rev Neurosci 5:97–107. https://doi.org/10.1038/nrn1327
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
Uylings HBM, Smit GJ, Veltman WAM (1975) Ordering methods in quantitative analysis of branching structures of dendritic trees. Adv Neurol 12:247–254
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
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
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
van Pelt J, Uylings HBM (2002) Branching rates and growth functions in the outgrowth of dendritic branching patterns. Network 13:261–281
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
Vetter P, Roth A, Häusser M (2001) Propagation of action potentials in dendrites depends on dendritic morphology. J Neurophysiol 85:926–937
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
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
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
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
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.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Nanda, S., Das, R., Bhattacharjee, S. et al. Morphological determinants of dendritic arborization neurons in Drosophila larva. Brain Struct Funct 223, 1107–1120 (2018). https://doi.org/10.1007/s00429-017-1541-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00429-017-1541-9