John Ewer

Genetic and Developmental Neurosciencejohn-ewer

Ph.D. Brandeis University (1991)
Associate Professor, Cornell University (2004)
Full Professor, Centro Interdisciplinario de Neurociencia de Valparaíso,
Facultad de Ciencias, Universidad de Valparaíso (2006-present).

Centro Milenio Genómica de la Célula (CGC)(2007)
Neurogenetics of Behavior and Development in Drosophila melanogaster
Director, Graduate program in Neurosciences
Curriculum Vitae

Contact information:

E-mail: john.ewer at uv.cl
Teléfono: 32-250-8143
Fax: 32-250-8027

Research Overview:

Regulation of Drosophila behavior by neuropeptides and the circadian clock

We use insect ecdysis to understand how neuropeptides and the circadian clock regulate animal behavior. Ecdysis is the behavior used by all insects to shed the remains of the old exoskeleton at the end of every molt. It is controlled by a number of neuropeptides and hormones, which regulate the precise order and timing of the different ecdysial behavioral subroutines. We use the molecular genetic tools available in Drosophila to identify the targets of these neuropeptides and hormones and to understand the contribution of each of these to the behavior; to visualize (using GCaMP, a calcium-sensitive GFP) neural activation during ecdysis; and to understand how this sequential behavior is produced. In collaboration with Ben White we have recently examined the response of all the neurons that are targets of ETH (Ecdysis Triggering Hormone), of one of the key neuropeptides that controls ecdysis (Diao et al., In press).
The final ecdysis to the adult, also called adult emergence, is controlled by the circadian clock, which restricts emergence to a specific window of time. This “gating” of emergence is known to depend on the activity of the central circadian pacemaker in the brain and on that of a peripheral clock located in the prothoracic gland, which produces the molting hormone, ecdysone. We use genetic approaches in Drosophila to understand how these pacemakers are coupled to produce a daily rhythm of emergence.

Degenerate control of ecdysis by neuropeptides CCAP and PBURS.

Degenerate control of ecdysis by neuropeptides CCAP and PBURS.   Failures at the ecdysis to the pupal stage cause the head to remain in the thorax and the wings and legs to be short (white arrow and black arrowheads in C and D, respectively).   (A) Flies mutant for CCAP expressed normal adult morphology.    By contrast, flies mutant for pburs (B) showed abnormalities at pupal ecdysis a well as in adult post-ecdysis (e.g., in wing inflation).   Interestingly, animals mutant for CCAP and pburs (C) showed a complete failure at pupal ecdysis, expressing defects that were more severe than those expressed by either mutant alone.    (D) Pharate control fly, showing a normal head, and normal wing and leg extension. See Lahr, Dean and Ewer (2012), for further details.

Ecdysis neuropeptides in mites

The recent completion of the spider mite genome (Grbic et al., 2011) offers a unique opportunity to investigate how ecdysis is controlled in this group of arthropods. Mites are chelicerates, a subphylum that includes mites, spiders, scorpions, and horseshow crabs and is, after insects, the most specious group of animals on earth. Our analysis of the spider mite genome revealed a striking degree of conservation in the ecdysis neuropeptides and hormones and their receptors when compared to those of insects, despite diverging from them several hundred million years ago. This work provides molecular tools to investigate the how ecdysis is controlled in mites. It will also allow for the rational development of acaricides to control this important group of agricultural pests and disease vectors.

Transmission electronmicrograph of the spidermite

Tetranychus urticae. Its genome is the first sequenced of a chelicerate.
See Grbic et al. (2011) for further details. Photo by Thomas Van Leeuwen and Wim Grunewald

Collaborations:

Benjamin White (National Institute of Mental Health, NIH, Bethesda, MD, USA.) Genetic analysis of neuropeptide action in Drosophila.
Website: http://www.nimh.nih.gov/labs-at-nimh/principal-investigators/benjamin-white.shtml

Christian Wegener (Biocenter, University of Würzburg, Würzburg, Germany). Circadian control of Drosophila emergence.
Website: http://www.neurogenetics.biozentrum.uni-wuerzburg.de/forschung/ag_wegener/christian_wegener/

Rob F. Jackson (Tufts University School of Medicine, Tufts University, Boston, USA). Circadian control of Drosophila emergence.
Website: http://sackler.tufts.edu/Academics/Degree-Programs/PhD-Programs/Faculty-Research-Pages/F-Rob-Jackson

Miodrag Grbic (University of Western Ontario, London, Canada); Analysis of spidermite genome.
Website: http://www.uwo.ca/biology/Faculty/grbicm/index.htm

Selected Publications

Refereed journal articles:

  • Selcho, M.[†], Millán, C.[†], Palacios-Muñoz, A. [†], Ruf, F., Ubillo, L., Chen, J., Bergmann, G., Ito, C., Silva, V., Wegener, C.[*], and Ewer, J.[*]. Central and peripheral clocks are coupled by a neuropeptide pathway in Drosophila. Nature Comm., In press. 
  • Mena, W., Diegelmann, S., Wegener, C., and Ewer, J. (2016). Stereotyped responses of Drosophila peptidergic neuronal ensemble depend on downstream neuromodulators. Elife 5., e19686. doi: 19610.17554/eLife.19686. 
  • Flaven-Pouchon, J., Farine, J.P., Ewer, J.[*], and Ferveur, J.F.[*] (2016). Regulation of cuticular hydrocarbon profile maturation by Drosophila tanning hormone, bursicon, and its interaction with desaturase activity. Insect Biochem Mol Biol 79:87-96., 10.1016/j.ibmb.2016.1010.1007. Epub 2016 Oct 1026.
  • Diao, F., Mena, W., Shi, J., Park, D., Diao, F., Taghert, P., Ewer, J., and White, B.H. (2016). The Splice Isoforms of the Drosophila Ecdysis Triggering Hormone Receptor Have Developmentally Distinct Roles. Genetics 202, 175-189. doi: 110.1534/genetics.1115.182121. Epub 182015 Nov 182123.
  • Krüger, E., Mena, W., Lahr, E.C., Johnson, E.C., and Ewer, J. (2015). Genetic analysis of Eclosion Hormone action during Drosophila larval ecdysis. Development, 142(24):4279-4287
  • Diao, F., H. Ironfield, H. Luan, F. Diao, W. C. Shropshire, J. Ewer, E. Marr, C. J. Potter, M. Landgraf and B. H. White (2015). Plug-and-Play Genetic Access to Drosophila Cell Types using Exchangeable Exon Cassettes. Cell Rep. 10(8): 1410-1421. doi: 1410.1016/j.celrep.2015.1401.1059. Epub 2015 Feb 1426.
  • Ardiles A, Ewer J, Acosta ML, Kirkwood A, Martinez A, Ebensperger LA, Bozinovic F, Lee TM, Palacios AG. (2013). Octodon degus (Molina 1782): A model in comparative biology and biomedicine. Cold Spring Harbor Protocols. pp. 312-18; doi:10.1101/pdb.emo071357
  • Lahr EC, Dean D, Ewer, J. (2012) Genetic analysis of ecdysis behavior in Drosophila reveals partially overlapping functions of two unrelated neuropeptides. Journal of  Neuroscience. 32(20):6819-29.
  • Sundram V, Fanny S, Ng FS, Roberts MA, Millán C, Ewer J, Jackson FR. (2012). Requirements for LARK in the Drosophila Circadian System. Journal of Biological Rhythms. 27(3):183-95.
  • Grbić, M., Van Leeuwen, Clark, R.M., Rombauts, S., Rouzé, P., el al. (2011). The genome of Tetranychus urticae reveals herbivorous pest adaptations. Nature 479: 487-492
  • Paré, A. C., D. M. Dean and J. Ewer (2009). “Construction and characterization of Deletions with defined endpoints in Drosophila using P-elements in trans.” Genetics. 181(1):53-63.
  • Luo C-W, Dewey EM, Sudo S, Ewer J, Hsu SY, Honegger H-W, Hsueh AJW. (2005). Bursicon, the insect cuticle hardening hormone, is a heterodimeric cystine knot protein that activates G protein-coupled receptor LGR2. Proc. Natl. Acad. Sci. USA 102:2820-2825.
  • Clark AC*, M.L. Del Campo*, and J. Ewer. (2004). Neuroendocrine control of larval ecdysis behavior in Drosophila: complex regulation by partially redundant neuropeptides. J. Neuroscience 24:4283-4292. (*) Co-first authors. Commentary: Casci, T. (2004). Shedding degeneracies. Nat. Rev. Genet. 5:488.
  • Husain Q.M. and J. Ewer. (2004). Use of targetable gfp-tagged neuropeptide for visualizing neuropeptide release following execution of a behavior in Drosophila. J. Neurobiol. 59:181-191.Park, J., A. J. Schroeder, C. Helfrich-Förster, F. R. Jackson and J. Ewer (2003). Targeted ablation of CCAP neuropeptide-containing neurons of Drosophila causes specific defects in execution and circadian timing of behavior. Development 130: 2645-2656.
  • Reviews:

  • Salazar, C., Valdivia, G., Ardiles, A.O., Ewer, J., and Palacios, A.G. (2016). Genetic variants associated with neurodegenerative Alzheimer disease in natural models. Biol Res 49:14., 10.1186/s40659-40016-40072-40659.
  • Aspé-Sanchez, M., Moreno, M., Rivera, M.I., Rossi, A., and Ewer, J. (2016). Oxytocin and Vasopressin Receptor Gene Polymorphisms: Role in Social and Psychiatric Traits. Front Neurosci 9:510., 10.3389/fnins.2015.00510. eCollection 02015.
  • Langenhan, T., Barr, M. M., Bruchas, M. R., Ewer, J., Griffith, L. C., Maiellaro, I., Taghert, P. H., White, B. H. and Monk, K. R. (2015). Model Organisms in GPCR Research. Mol Pharmacol 15(115): 098764.
  • Ewer, J., Jindra, M. (2014). Editorial overview: Development and regulation: Departing from paradigms. Curr. Op. Insect Sci. 1: vii-ix.
  • White, B.H., and Ewer, J. (2014) Neural and Hormonal Control of Postecdysial Behaviors in Insects. Ann. Rev. Entomol. 59:363-81
  • Honegger, H. W., E. M. Dewey and Ewer J. (2008). “Bursicon, the tanning hormone of insects: recent advances following the discovery of its molecular identity.” J Comp Physiol A. 194: 989-1005
  • Ewer, J. (2007) The Neuroendocrinology of eclosion. In: Invertebrate Neurobiology, Greenspan, R., and North, G., Eds. Cold Spring Harbor Press. P 555-579. 
  • Ewer, J. (2005) Behavioral actions of neuropeptides in invertebrates: insights from Drosophila. Horm Behav. 48:418-429.