Statistical Characterization, Modelling and Classification of Morphological Changes in imp Mutant Drosophila Gamma Neurons

A. Razetti, X. Descombes, C. Medioni, F. Besse

Abstract

In Drosophila brain, gamma neurons in the mushroom body are involved in higher functions such as olfactory learning and memory. During metamorphosis, they undergo remodelling after which they adopt their adult shape. Some mutations alter remodelling and therefore neuronal final morphology, causing behavioural dysfunctions. The RNA binding protein Imp, for example, was shown to control this remodelling process at least partly by regulating profilin expression. This work aims at precisely characterizing the morphological changes observed upon imp knockdown in order to further understand the role of this protein. We develop a methodological framework that consists in the selection of relevant morphological features, their modelling and parameter estimation. We thus perform a statistical comparison and a likelihood analysis to quantify similarities and differences between wild type and mutated neurons. We show that imp mutant neurons can be classified into two phenotypic groups (called Imp L and Imp Sh) that differ in several morphological aspects. We also demonstrate that, although Imp L and wild-type neurons show similarities, branch length distribution is discriminant between these populations. Finally, we study biological samples in which Profilin was reintroduced in imp mutant neurons, and show that defects in main axon and branch lengths are partially suppressed.

References

  1. Forbes, C., Evans, M., Hastings, N., and Peacock, B., 2011. Statistical distributions, John Wiley & Sons, 4th edition.
  2. Guerra, L., McGarry, L. M., Robles, V., Bielza, C., Larranaga, P., & Yuste, R., 2011. Comparison between supervised and unsupervised classifications of neuronal cell types: a case study. Developmental neurobiology, 71(1), 71-82.
  3. Keller, M.T. and Trotter, W.T., 2015. Applied Combinatorics. Georgia Institute of Technology, Preliminary Edition.
  4. Kemeny, J. G., and Snell, J. L., 1960. Finite markov chains, vol. 356. van Nostrand, 1st edition.
  5. Kong, J. H., Fish, D. R., Rockhill, R. L., and Masland, R. H., 2005. Diversity of ganglion cells in the mouse retina: unsupervised morphological classification and its limits. J. of Comp. Neurology, 489(3), 293-310.
  6. López-Cruz, P. L., Larrañaga, P., DeFelipe, J., and Bielza, C., 2014. Bayesian network modeling of the consensus between experts: An application to neuron classification. Int. J. of Approx. Reasoning, 55(1), 3-22.
  7. Luo, L., 2002. Actin cytoskeleton regulation in neuronal morphogenesis and structural plasticity. Annual review of cell and developmental biology, 18(1), 601-635.
  8. Medioni, C., Ramialison, M., Ephrussi, A., and Besse, F., 2014. Imp promotes axonal remodeling by regulating profilin mRNA during brain development. Current Biology, 24(7), 793-800.
  9. Mottini, A., Descombes, X., and Besse, F., 2013. Tree-like shapes distance using the elastic shape analysis framework. In British Machine Vision Conference.
  10. Mottini, A., Descombes, X., Besse, F., and Pechersky, E., 2014. Discrete stochastic model for the generation of axonal trees. In EMBS, 6814-6817.
  11. Mottini A, Descombes X., and Besse F., 2014. From Curves to Trees: A Tree-like Shapes Distance Using the Elastic Shape Analysis Framework. Neuroinformatics, 13, 175-191.
  12. Myatt, D. R., Hadlington, T., Ascoli, G. A., and Nasuto, S. J., 2012. Neuromantic-from semi-manual to semiautomatic reconstruction of neuron morphology. Frontiers in neuroinformatics, 6.
  13. Redt Clouet, C et al., 2012. Mushroom body neuronal remodelling is necessary for short term but not for long term courtship memory in Drosophila. European Journal of Neuroscience, 35(11), 1684-1691.
  14. Schindelin, J et al, 2012. Fiji: an open-source platform for biological-image analysis. Nature meth.9(7), 676-682.
  15. Schlüter, K., Jockusch, B. M., and Rothkegel, M., 1997. Profilins as regulators of actin dynamics. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1359(2), 97-109.
  16. Szebenyi, G., Callaway, J. L., Dent, E. W., and Kalil, K., 1998. Interstitial branches develop from active regions of the axon demarcated by the primary growth cone during pausing behaviours. The Journal of neuroscience, 18(19), 7930-7940.
  17. Tessier, C. R., and Broadie, K., 2008. Drosophila fragile X mental retardation protein developmentally regulates activity-dependent axon pruning. Development, 135(8), 1547-1557.
  18. Verheyen, E. M., and Cooley, L., 1994. Profilin mutations disrupt multiple actin-dependent processes during Drosophila development. Development, 120(4), 717- 728.
  19. Williams, D. W., and Truman, J. W., 2005. Remodeling dendrites during insect metamorphosis. Journal of neurobiology, 64(1), 24-33.
  20. Wu, J. S., and Luo, L., 2006. A protocol for mosaic analysis with a repressible cell marker (MARCM) in Drosophila. Nature protocols, 1(6), 2583-2589.
  21. Xie, Z., Huang, C., Ci, B., Wang, L., and Zhong, Y., 2013. Requirement of the combination of mushroom body ? lobe and a/ß lobes for the retrieval of both aversive and appetitive early memories in Drosophila. Learning & Memory,20(9), 474-481.
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Paper Citation


in Harvard Style

Razetti A., Descombes X., Medioni C. and Besse F. (2016). Statistical Characterization, Modelling and Classification of Morphological Changes in imp Mutant Drosophila Gamma Neurons . In Proceedings of the 9th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 3: BIOINFORMATICS, (BIOSTEC 2016) ISBN 978-989-758-170-0, pages 63-74. DOI: 10.5220/0005703800630074


in Bibtex Style

@conference{bioinformatics16,
author={A. Razetti and X. Descombes and C. Medioni and F. Besse},
title={Statistical Characterization, Modelling and Classification of Morphological Changes in imp Mutant Drosophila Gamma Neurons},
booktitle={Proceedings of the 9th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 3: BIOINFORMATICS, (BIOSTEC 2016)},
year={2016},
pages={63-74},
publisher={SciTePress},
organization={INSTICC},
doi={10.5220/0005703800630074},
isbn={978-989-758-170-0},
}


in EndNote Style

TY - CONF
JO - Proceedings of the 9th International Joint Conference on Biomedical Engineering Systems and Technologies - Volume 3: BIOINFORMATICS, (BIOSTEC 2016)
TI - Statistical Characterization, Modelling and Classification of Morphological Changes in imp Mutant Drosophila Gamma Neurons
SN - 978-989-758-170-0
AU - Razetti A.
AU - Descombes X.
AU - Medioni C.
AU - Besse F.
PY - 2016
SP - 63
EP - 74
DO - 10.5220/0005703800630074