Zentrale Abteilung für Elektronenmikroskopie - Imaging Core Facility

Research: Synaptic architecture at the nano-scale

Neuronal synapses are highly efficient and complex cellular signaling machineries that achieve remarkable precision in signal transmission for a prolonged period of time, in some cases throughout the lifetime of an animal. The importance of synaptic efficiency is mirrored by many neural diseases but in particular by synaptopathies where synaptic organization and function is disrupted. In order to provide reliable signaling synaptic vesicles have to be retained close to the presynaptic active zone, the domain where vesicles are docked and fuse with the membrane after Ca influx in a nano-domain through voltage gated channels.
How are synaptic vesicles kept coherently close to the active zone to maintain efficient signaling? To shed light onto this question our team focuses on the cellular architecture using a combination of genetic tools and imaging techniques. In particular we apply electron tomography as ultra high 3D resolution method to dissect components and function of synaptic architecture. We use a synergistic combination of two highly tractable models where they are most appropriate: The C. elegans neuromuscular junctions for efficient candidate identification and manipulation and the neuromuscular junctions of the zebrafish larva as vertebrate model to test for evolutionary conservation of function.

List of publications Frederik Helmprobst

1) Expression of sept3, sept5a and sept5b in the Developing and Adult Nervous System of the Zebrafish (Danio rerio)
Helmprobst F, Lillesaar C, Stigloher C.
Frontiers in Neuroanatomy, 2017 Feb 17,  11, 6

2) FIJI Macro 3D ART VeSElecT: 3D Automated Reconstruction Tool for Vesicle Structures of Electron Tomograms.
Kaltdorf KV, Schulze K, Helmprobst F, Kollmannsberger P, Dandekar T*, Stigloher C*.  
PLoS Computational Biology, 2017 Jan 5, 13(1):e1005317.

3) Presynaptic architecture of the larval zebrafish neuromuscular junction.
Helmprobst F, Frank M, Stigloher C.
J Comp Neurol, 2015 Sep 1;523(13):1984-97.  

List of publications Sebastian Markert

1) Shedding light on cell compartmentation in the candidate phylum Poribacteria by high resolution visualisation and transcriptional profiling.
Jahn MT, Markert SM, Ryu T, Ravasi T, Stigloher C, Hentschel U, Moitinho-Silva L.
Sci Rep. 2016 Oct 31;6:35860. doi: 10.1038/srep35860.

2) Filling the gap: adding super-resolution to array tomography for correlated ultrastructural and molecular identification of electrical synapses at the C. elegans connectome.
Markert SM, Britz S, Proppert S, Lang M, Witvliet D, Mulcahy B, Sauer M, Zhen M, Bessereau JL, Stigloher C.
Neurophotonics. 2016 Oct;3(4):041802. doi: 10.1117/1.NPh.3.4.041802. Epub 2016 May 4.

3) ‘Y’Scenedesmus (Chlorophyta, Chlorophyceae): the internal transcribed spacer 2 rRNA secondary structure re-revisited.
Markert SM, Müller T, Koetschan C, Friedl T, Wolf M.
Plant Biology, 2012 May 28;14(6):987-96.

4) Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei.
Batram C, Jones NG, Janzen CJ, Markert SM, Engstler M.
eLife, 2014 May 20;3:e02324.

List of publications Christian Stigloher

1) Expression of sept3, sept5a and sept5b in the Developing and Adult Nervous System of the Zebrafish (Danio rerio)
Helmprobst F, Lillesaar C, Stigloher C.
Frontiers in Neuroanatomy, 2017 Feb 17,  11, 6

2) FIJI Macro 3D ART VeSElecT: 3D Automated Reconstruction Tool for Vesicle Structures of Electron Tomograms.
Kaltdorf KV, Schulze K, Helmprobst F, Kollmannsberger P, Dandekar T*, Stigloher C*.  
PLoS Computational Biology, 2017 Jan 5, 13(1):e1005317.

3) Shedding light on cell compartmentation in the candidate phylum Poribacteria by high resolution visualisation and transcriptional profiling.
Jahn MT, Markert SM, Ryu T, Ravasi T, Stigloher C, Hentschel U, Moitinho-Silva L.
Sci Rep. 2016 Oct 31;6:35860. doi: 10.1038/srep35860.

4) Distribution of the obligate endosymbiont Blochmannia floridanus and expression analysis of putative immune genes in ovaries of the carpenter ant Camponotus floridanus.
Kupper M, Stigloher C, Feldhaar H, Gross R.
Arthropod Struct Dev. 2016 Sep 21. pii: S1467-8039(16)30032-9. doi: 10.1016/j.asd.2016.09.004. [Epub ahead of print]

5) Filling the gap: adding super-resolution to array tomography for correlated ultrastructural and molecular identification of electrical synapses at the C. elegans connectome.
Markert SM, Britz S, Proppert S, Lang M, Witvliet D, Mulcahy B, Sauer M, Zhen M, Bessereau JL, Stigloher C.
Neurophotonics. 2016 Oct;3(4):041802. doi: 10.1117/1.NPh.3.4.041802. Epub 2016 May 4.

6) Autophagic digestion of Leishmania major by host macrophages is associated with differential expression of BNIP3, CTSE, and the miRNAs miR-101c, miR-129, and miR-210.
Frank B, Marcu A, de Oliveira Almeida Petersen AL, Weber H, Stigloher C, Mottram JC, Scholz CJ, Schurigt U.
Parasit Vectors, 2015 Jul 31;8:404. 

7) Presynaptic architecture of the larval zebrafish neuromuscular junction.
Helmprobst F, Frank M, Stigloher C.
J Comp Neurol, 2015 Sep 1;523(13):1984-97. 

8) Intrinsically disordered and pliable Starmaker-like protein from medaka (Oryzias latipes) controls the formation of calcium carbonate crystals.
Różycka M, Wojtas M, Jakób M, Stigloher C, Grzeszkowiak M, Mazur M, Ożyhar A.
PLoS One, 2014 Dec 9;9(12):e114308. 

9) In vivo single-molecule imaging identifies altered dynamics of calcium channels in dystrophin-mutant C. elegans.
Zhan H, Stanciauskas R, Stigloher C, Dizon KK, Jospin M, Bessereau JL, Pinaud F.
Nat Commun, 2014 Sep 18;5:4974.

10) C. elegans Punctin specifies cholinergic versus GABAergic identity of postsynaptic domains.
Pinan-Lucarré B, Tu H, Pierron M, Cruceyra PI, Zhan H, Stigloher C, Richmond JE, Bessereau JL.
Nature, 2014 Jul 24;511(7510):466-70.

11) Attenuation of insulin signalling contributes to FSN-1-mediated regulation of synapse development.
Hung WL, Hwang C, Gao S, Liao EH, Chitturi J, Wang Y, Li H, Stigloher C, Bessereau JL, Zhen M.
EMBO J, 2013 Jun 12;32(12):1745-60.

12) Positive modulation of a Cys-loop acetylcholine receptor by an auxiliary trans-membrane subunit.
Boulin T, Rapti G, Briseno-Roa L, Stigloher C, Richmond JE, Paoletti P, Bessereau JL.
Nature Neuroscience
, 2012 Oct 15(10):1374-1381.

13) Expression of hairy/enhancer of split genes in neural progenitors and neurogenesis domains of the adult zebrafish brain
Chapouton P*, Webb JK*, Stigloher C*, Alunni A, Adolf B, Hesl B, Topp S, Kremmer E and Bally-Cuif L
Journal of Comparative Neurology
, 2011 Jun 15;519(9):1748-69.

14) The Enhancer of split transcription factor Her8a is a novel dimerisation partner for Her3 that controls anterior hindbrain neurogenesis in zebrafish.
Webb KJ, Coolen M, Gloeckner CJ, Stigloher C, Bahn B, Topp S, Ueffing M, Bally-Cuif L.
BMC Dev Biol
, 2011 May 17;11(1):27.

15) The Presynaptic Dense Projection of the Caenorhabiditis elegans Cholinergic Neuromuscular Junction Localizes Synaptic Vesicles at the Active Zone through SYD-2/Liprin and UNC-10/RIM-Dependent Interactions.
Stigloher C
, Zhan H., Zhen M., Richmond JE, Bessereau JL.
Journal of Neuroscience
, 2011 Mar 23;31(12):4388-96.

16) Axonal projections originating from raphe serotonergic neurons in the developing and adult zebrafish, Danio rerio, using transgenics to visualize raphe-specific pet1 expression.
Lillesaar C, Stigloher C, Tannhäuser B, Wullimann MF, Bally-Cuif L.
Journal of Comparative Neurology
, 2009 Jan 10; 512(2):158-82.

17) Pleiotropic effects in Eya3 knockout mice.
Söker T, Dalke C, Puk O, Floss T, Becker L, Bolle I, Favor J, Hans W, Hölter SM, Horsch M, Kallnik M, Kling E, Moerth C, Schrewe A, Stigloher C, Topp S, Gailus-Durner V, Naton B, Beckers J, Fuchs H, Ivandic B, Klopstock T, Schulz H, Wolf E, Wurst W, Bally-Cuif L, de Angelis MH, Graw J.
BMC Developmental Biology
, 2008 Dec 22; 8:118.

18) Fgf signaling in the zebrafish adult brain: association of Fgf activity with ventricular zones but not cell proliferation.
Topp S, Stigloher C, Komisarczuk AZ, Adolf B, Becker TS, Bally-Cuif L.
Journal of Comparative Neurology
, 2008 Oct 1; 510(4):422-39.

19) Enhancer detection and developmental expression of zebrafish sprouty1, a member of the fgf8 synexpression group.
Komisarczuk AZ, Topp S, Stigloher C, Kapsimali M, Bally-Cuif L, Becker TS.
Developmental Dynamics
, 2008 Sep; 237(9):2594-603.

20) Gsk3beta/PKA and Gli1 regulate the maintenance of neural progenitors at the midbrain-hindbrain boundary in concert with E(Spl) factor activity.
Ninkovic J*, Stigloher C*, Lillesaar C*, Bally-Cuif L.
Development,
 2008 Sep; 135(18):3137-48.

21) MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary.
Leucht C*, Stigloher C*, Wizenmann A, Klafke R, Folchert A, Bally-Cuif L.
Nature Neuroscience
, 2008 Jun; 11(6):641-8.

22) Identification of neural progenitor pools by E(Spl) factors in the embryonic and adult brain.
Stigloher C
, Chapouton P, Adolf B, Bally-Cuif L.
Brain Research Bulletin
, 2008 Mar 18; 75(2-4):266-73. Review.

23) The serotonergic phenotype is acquired by converging genetic mechanisms within the zebrafish central nervous system.
Lillesaar C, Tannhäuser B, Stigloher C, Kremmer E, Bally-Cuif L.
Developmental Dynamics
, 2007 Apr; 236(4):1072-84.

24) Segregation of telencephalic and eye-field identities inside the zebrafish forebrain territory is controlled by Rx3.
Stigloher C
, Ninkovic J, Laplante M, Geling A, Tannhäuser B, Topp S, Kikuta H, Becker TS, Houart C, Bally-Cuif L.
Development
, 2006 Aug; 133(15):2925-35. 

S. Britz, V. Perschin, S. Tröger, K. Kaltdorf, S. Markert, C. Stigloher, F. Helmprobst, M. Strobel
Hubland Süd, Geb. B1 Hubland Nord, Geb. 32 Julius-von-Sachs-Platz 2 Fabrikschleichach Hubland Süd, Geb. B2 Campus Medizin