Prof. Dr. Joachim Wittbrodt
My papers are now all open access. All manuscripts that I sign as corresponding author are pre-print submissions at the point of review.
Current Pre-Print Submissions
Instantaneous isotropic volumetric imaging of fast biological processes
Nils Wagner, Nils Norlin, Jakob Gierten, Gustavo de Medeiros, Bálint Balázs, Joachim Wittbrodt, Lars Hufnagel, Robert Prevedel
bioRxiv 459370; doi: https://doi.org/10.1101/459370
Jakob Gierten, Christian Pylatiuk, Omar T Hammouda, Christian Schock, Johannes Stegmaier, Joachim Wittbrodt, Jochen Gehrig, Felix Loosli.
Recent Key Publications
Weinhardt V, Shkarin R, Wernet T, Wittbrodt J, Baumbach T, Loosli F. (2018). Quantitative morphometric analysis of adult teleost fish by X-ray computed tomography. Sci Rep. 8(1):16531. Abstract Vertebrate models provide indispensable paradigms to study development and disease. Their analysis requires a quantitative morphometric study of the body, organs and tissues. This is often impeded by pigmentation and sample size. X-ray micro-computed tomography (micro-CT) allows high-resolution volumetric tissue analysis, largely independent of sample size and transparency to visual light. Importantly, micro-CT data are inherently quantitative. We report a complete pipeline of high-throughput 3D data acquisition and image analysis, including tissue preparation and contrast enhancement for micro-CT imaging down to cellular resolution, automated data processing and organ or tissue segmentation that is applicable to comparative 3D morphometrics of small vertebrates. Applied to medaka fish, we first create an annotated anatomical atlas of the entire body, including inner organs as a quantitative morphological description of an adult individual. This atlas serves as a reference model for comparative studies. Using isogenic medaka strains we show that comparative 3D morphometrics of individuals permits identification of quantitative strain-specific traits. Thus, our pipeline enables high resolution morphological analysis as a basis for genotype-phenotype association studies of complex genetic traits in vertebrates.
Gutierrez-Triana JA*, Tavhelidse T*, Thumberger T*, Thomas I, Wittbrodt B, Kellner T, Anlas K, Tsingos E, Wittbrodt J. (2018). Efficient single-copy HDR by 5' modified long dsDNA donors. Elife. 7. pii: e39468.
*Equal contribution
Lust K, Wittbrodt J. (2018). Activating the regenerative potential of Müller glia cells in a regeneration-deficient retina. eLife. 7. pii: e32319.
Abstract
Inoue D*, Stemmer M, Thumberger T, Ruppert T, Bärenz F, Wittbrodt J*, Gruss OJ*. (2017). Expression of the novel maternal centrosome assembly factor Wdr8 is required for vertebrate embryonic mitoses. Nat Commun. 8:14090. DOI: 10.1038/ncomms14090
2019
Tsingos E, Höckendorf B, Sütterlin T, Kirchmaier S, Grabe N, Centanin L, Wittbrodt J. (2019). Retinal stem cells modulate proliferative parameters to coordinate post-embryonic morphogenesis in the eye of fish. Elife. 8. pii: e42646.Eckert P, Knickmeyer MD, Schütz L, Wittbrodt J, Heermann S. (2019). Morphogenesis and axis specification occur in parallel during optic cup and optic fissure formation, differentially modulated by BMP and Wnt. Open Biol. 9(2):180179.



2018
Weinhardt V, Shkarin R, Wernet T, Wittbrodt J, Baumbach T, Loosli F. (2018). Quantitative morphometric analysis of adult teleost fish by X-ray computed tomography. Sci Rep. 8(1):16531.
Gutierrez-Triana JA*, Tavhelidse T*, Thumberger T*, Thomas I, Wittbrodt B, Kellner T, Anlas K, Tsingos E, Wittbrodt J. (2018). Efficient single-copy HDR by 5' modified long dsDNA donors. Elife. 7. pii: e39468.
*Equal contribution

Knickmeyer MD(1)(2), Mateo JL(3), Eckert P(1)(2), Roussa E(1), Rahhal B(1), Zuniga A(4), Krieglstein K(1), Wittbrodt J(5), Heermann S(6). TGFβ-facilitated optic fissure fusion and the role of bone morphogenetic protein antagonism.


Lust K, Wittbrodt J. (2018). Activating the regenerative potential of Müller glia cells in a regeneration-deficient retina. eLife. 7. pii: e32319. DOI: 10.7554/eLife.32319

Abstract
2017
Stemmer M, Thumberger T, Del Sol Keyer M, Wittbrodt J, Mateo JL. (2017). Correction: CCTop: An Intuitive, Flexible and Reliable CRISPR/Cas9 Target Prediction Tool. PLoS One. 12(4):e0176619.
Inoue D*, Stemmer M, Thumberger T, Ruppert T, Bärenz F, Wittbrodt J*, Gruss OJ*. (2017). Expression of the novel maternal centrosome assembly factor Wdr8 is required for vertebrate embryonic mitoses. Nat Commun. 8:14090. DOI: 10.1038/ncomms14090

2016
Gutierrez-Triana JA, Mateo JL, Ibberson D, Ryu S, Wittbrodt J. (2016). iDamIDseq and iDEAR: an improved method and computational pipeline to profile chromatin-binding proteins. Development. 143(22):4272-4278. DOI:10.1242/dev.139261




Alonso-Barba JI, Rahman RU, Wittbrodt J, Mateo JL. (2016). MEPD: medaka expression pattern database, genes and more. Nucleic Acids Res. 2016 Jan 4;44(D1):D819-21. doi: 10.1093/nar/gkv1029.

Lust K, Wittbrodt J. (2015) Hold your breath. Elife. 2015 Dec 16;4:e12523. doi: 10.7554/eLife.12523.

Zhang P, Kratz AS, Salama M, Elabd S, Heinrich T, Wittbrodt J, Blattner C, Davidson G. (2015). Expression screening using a Medaka cDNA library identifies evolutionarily conserved regulators of the p53/Mdm2 pathway. BMC Biotechnol. 15(1):92.
Beccari L, Marco-Ferreres R, Tabanera N, Manfredi A, Souren M, Wittbrodt B, Conte I, Wittbrodt J, Bovolenta P. (2015). A trans-regulatory code for the forebrain expression of Six3.2 in the medaka fish. J Biol Chem. 2015 Sep 16. pii: jbc.M115.681254. [

Bajoghli B, Kuri P, Inoue D, Aghaallaei N, Hanelt M, Thumberger T, Rauzi M, Wittbrodt J, Leptin M. (2015). Noninvasive In Toto Imaging of the Thymus Reveals Heterogeneous Migratory Behavior of Developing T Cells. J Immunol. 195(5):2177-86.

Auer TO, Xiao T, Bercier V, Gebhardt V, Duroure K, Concordet J-P, Wyart C, Suster M, Kawakami K, Wittbrodt J, Baier H, Del Bene F. (2015). Deletion of a kinesin I motor unmasks a mechanism of homeostatic branching control by neurotrophin-3. eLIFE. 4:e05061.
Stemmer M, Thumberger T, Del Sol Keyer M, Wittbrodt J, Mateo JL. (2015). CCTop: An Intuitive, Flexible and Reliable CRISPR/Cas9 Target Prediction Tool. PLoS One. 10(4):e0124633.
Reinhardt R, Centanin L, Tavhelidse T, Inoue D, Wittbrodt B, Concordet JP, Martinez-Morales JR, Wittbrodt J. (2015). Sox2, Tlx, Gli3, and Her9 converge on Rx2 to define retinal stem cells in vivo. EMBO J. 2015 Apr 23. pii: e201490706.

Zhang P, Elabd S, Hammer S, Solozobova V, Yan H, Bartel F, Inoue S, Henrich T, Wittbrodt J, Loosli F, Davidson G, Blattner C. (2015). TRIM25 has a dual function in the p53/Mdm2 circuit. 1. Oncogene. 2015 Mar 2.
Heermann S, Schütz L, Lemke S, Krieglstein K, Wittbrodt J. (2015). Eye morphogenesis driven by epithelial flow into the optic cup facilitated by modulation of bone morphogenetic protein. eLIFE. 4:e05216.
Stemmer M, Schuhmacher LN, Foulkes NS, Bertolucci C, Wittbrodt J. (2015). Cavefish eye loss in response to an early block in retinal differentiation progression. Development. 142:743-752.
2014
Chen Q, Su Y, Wesslowski J, Hagemann AI, Ramialison M, Wittbrodt J, Scholpp S, Davidson G. (2014). Tyrosine phosphorylation of LRP6 by Src and Fer inhibits Wnt/β-catenin signalling. 1. EMBO Rep. 2014 Nov 12. pii: e201439644.


Crespo CL, Vernieri C, Keller PJ, Garrè M, Bender JR, Wittbrodt J, Pardi R. (2014). The PAR complex controls the spatiotemporal dynamics of F-actin and the MTOC in directionally migrating leukocytes. J Cell Sci. 127(20): 4381-4395.
Abstract
Inflammatory cells acquire a polarized phenotype to migrate toward sites of infection or injury. A conserved polarity complex comprising PAR-3, PAR-6, and atypical protein kinase C (aPKC) relays extracellular polarizing cues to control cytoskeletal and signaling networks affecting morphological and functional polarization. Yet, there is no evidence that myeloid cells use PAR signaling to migrate vectorially in 3D environments in vivo. Using genetically-encoded bioprobes and high-resolution live imaging we revealed the existence of F-actin oscillations in the trailing edge and constant MTOC repositioning to direct leukocyte migration in wounded medaka fish larvae. Genetic manipulation in live myeloid cells demonstrated that the catalytic activity of aPKC and the regulated interaction with PAR-3/PAR-6 are required for consistent F- actin oscillations, MTOC perinuclear mobility, aPKC repositioning and wound-directed migration upstream of Rho-kinase/ROCK/ROK activation. We propose that the PAR complex coordinately controls cytoskeletal changes affecting both traction force generation and directionality of leukocyte migration to sites of injury.
Sinn R, Peravali R, Heermann S, Wittbrodt J. (2014). Differential responsiveness of distinct retinal domains to Atoh7. 2. Mech Dev. 2014 Aug 21. pii: S0925-4773(14)00038-0.
Abstract
Centanin L, Ander JJ, Hoeckendorf B, Lust K, Kellner T, Kraemer I, Urbany C, Hasel E, Harris WA, Simons BD, Wittbrodt J. (2014). Exclusive multipotency and preferential asymmetric divisions in post-embryonic neural stem cells of the fish retina. Development. 141(18):3472-82.
Abstract
The potency of post-embryonic stem cells can only be addressed in the living organism, by labeling single cells after embryonic development and following their descendants. Recently, transplantation experiments involving permanently labeled cells revealed multipotent neural stem cells (NSCs) of embryonic origin in the medaka retina. To analyze whether NSC potency is affected by developmental progression, as reported for the mammalian brain, we developed an inducible toolkit for clonal labeling and non-invasive fate tracking. We used this toolkit to address post-embryonic stem cells in different tissues and to functionally differentiate transient progenitor cells from permanent, bona fide stem cells in the retina. Using temporally controlled clonal induction, we showed that post-embryonic retinal NSCs are exclusively multipotent and give rise to the complete spectrum of cell types in the neural retina. Intriguingly, and in contrast to any other vertebrate stem cell system described so far, long-term analysis of clones indicates a preferential mode of asymmetric cell division. Moreover, following the behavior of clones before and after external stimuli, such as injuries, shows that NSCs in the retina maintained the preference for asymmetric cell division during regenerative responses. We present a comprehensive analysis of individual post-embryonic NSCs in their physiological environment and establish the teleost retina as an ideal model for studying adult stem cell biology at single cell resolution.
Mazaheri F, Breus O, Durdu S, Haas P, Wittbrodt J, Gilmour D, Peri F. (2014). Distinct roles for BAI1 and TIM-4 in the engulfment of dying neurons by microglia. Nat Commun. 5:4046.
Abstract
The removal of dying neurons by microglia has a key role during both development and in several diseases. To date, little is known about the cellular and molecular processes underlying neuronal engulfment in the brain. Here we took a live imaging approach to quantify neuronal cell death progression in embryonic zebrafish brains and studied the response of microglia. We show that microglia engulf dying neurons by extending cellular branches that form phagosomes at their tips. At the molecular level we found that microglia lacking the phosphatidylserine receptors BAI1 and TIM-4, are able to recognize the apoptotic targets but display distinct clearance defects. Indeed, BAI1 controls the formation of phagosomes around dying neurons and cargo transport, whereas TIM-4 is required for phagosome stabilization. Using this single-cell resolution approach we established that it is the combined activity of BAI1 and TIM-4 that allows microglia to remove dying neurons.
Spivakov M, Auer TO, Peravali R, Dunham I, Dolle D, Fujiyama A, Toyoda A, Aizu T, Minakuchi Y, Loosli F, Naruse K, Birney E, Wittbrodt J. (2014). Genomic and Phenotypic Characterization of a Wild Medaka Population: Towards the Establishment of an Isogenic Population Genetic Resource in Fish. 1. G3 (Bethesda). 2014 Jan 9. pii: g3.113.008722v1.
Centanin L, Wittbrodt J. (2014). Retinal neurogenesis. Development. 141(2):241-4.
2013
Müller C, Maeso I, Wittbrodt J, Martínez-Morales JR. (2013). The medaka mutation tintachina sheds light on the evolution of V-ATPase B subunits in vertebrates. Sci Rep. 3:3217.
Abstract
Vacuolar-type H(+) ATPases (V-ATPases) are multimeric protein complexes that play a universal role in the acidification of intracellular compartments in eukaryotic cells. We have isolated the recessive medaka mutation tintachina (tch), which carries an inactivating modification of the conserved glycine residue (G75R) of the proton pump subunit atp6v1Ba/vatB1. Mutant embryos show penetrant pigmentation defects, massive brain apoptosis and lethality before hatching. Strikingly, an equivalent mutation in atp6v1B1 (G78R) has been reported in a family of patients suffering from distal renal tubular acidosis (dRTA), a hereditary disease that causes metabolic acidosis due to impaired kidney function. This poses the question as to how molecularly identical mutations result in markedly different phenotypes in two vertebrate species. Our work offers an explanation for this phenomenon. We propose that, after successive rounds of whole-genome duplication, the emergence of paralogous copies allowed the divergence of the atp6v1B cis-regulatory control in different vertebrate groups.
Kirchmaier S, Lust K, Wittbrodt J. (2013). Golden GATEway Cloning - A Combinatorial Approach to Generate Fusion and Recombination Constructs. PLoS One. 8(10):e76117.
Abstract
The design and generation of DNA constructs is among the necessary but generally tedious tasks for molecular biologists and, typically, the cloning strategy is restricted by available restriction sites. However, increasingly sophisticated experiments require increasingly complex DNA constructs, with an intricacy that exceeds what is achievable using standard cloning procedures. Many transgenes such as inducible gene cassettes or recombination elements consist of multiple components that often require precise in-frame fusions. Here, we present an efficient protocol that facilitates the generation of these complex constructs. The golden GATEway cloning approach presented here combines two established cloning methods, namely golden Gate cloning and Multisite Gateway(TM) cloning. This allows efficient and seamless assembly as well as reuse of predefined DNA elements. The golden Gate cloning procedure follows clear and simple design rules and allows the assembly of multiple fragments with different sizes into one open reading frame. The final product can be directly integrated into the widely used Multisite Gateway(TM) cloning system, granting more flexibility when using a transgene in the context of multiple species. This adaptable and streamlined cloning procedure overcomes restrictions of "classical construct generation" and allows focusing on construct design.
Kirchmaier S, Höckendorf B, Möller EK, Bornhorst D, Spitz F, Wittbrodt J. (2013). Efficient site-specific transgenesis and enhancer activity tests in medaka using PhiC31 integrase. Development. 140(20):4287-95.
Abstract
Established transgenesis methods for fish model systems allow efficient genomic integration of transgenes. However, thus far a way of controlling copy number and integration sites has not been available, leading to variable transgene expression caused by position effects. The integration of transgenes at predefined genomic positions enables the direct comparison of different transgenes, thereby improving time and cost efficiency. Here, we report an efficient PhiC31-based site-specific transgenesis system for medaka. This system includes features that allow the pre-selection of successfully targeted integrations early on in the injected generation. Pre-selected embryos transmit the correctly integrated transgene through the germline with high efficiency. The landing site design enables a variety of applications, such as reporter and enhancer switch, in addition to the integration of any insert. Importantly, this allows assaying of enhancer activity in a site-specific manner without requiring germline transmission, thus speeding up large-scale analyses of regulatory elements.
Martynoga B, Mateo JL, Zhou B, Andersen J, Achimastou A, Urbán N, van den Berg D, Georgopoulou D, Hadjur S, Wittbrodt J, Ettwiller L, Piper M, Gronostajski RM, Guillemot F. (2013). Epigenomic enhancer annotation reveals a key role for NFIX in neural stem cell quiescence. Genes Dev. 27(16):1769-86.
Abstract
The majority of neural stem cells (NSCs) in the adult brain are quiescent, and this fraction increases with aging. Although signaling pathways that promote NSC quiescence have been identified, the transcriptional mechanisms involved are mostly unknown, largely due to lack of a cell culture model. In this study, we first demonstrate that NSC cultures (NS cells) exposed to BMP4 acquire cellular and transcriptional characteristics of quiescent cells. We then use epigenomic profiling to identify enhancers associated with the quiescent NS cell state. Motif enrichment analysis of these enhancers predicts a major role for the nuclear factor one (NFI) family in the gene regulatory network controlling NS cell quiescence. Interestingly, we found that the family member NFIX is robustly induced when NS cells enter quiescence. Using genome-wide location analysis and overexpression and silencing experiments, we demonstrate that NFIX has a major role in the induction of quiescence in cultured NSCs. Transcript profiling of NS cells overexpressing or silenced for Nfix and the phenotypic analysis of the hippocampus of Nfix mutant mice suggest that NFIX controls the quiescent state by regulating the interactions of NSCs with their microenvironment.
Schaafhausen MK, Yang WJ, Centanin L, Wittbrodt J, Bosserhoff A, Fischer A, Schartl M, Meierjohann S. (2013). Tumor angiogenesis is caused by single melanoma cells in a manner dependent on reactive oxygen species and NF-κB. J Cell Sci. 126(Pt 17):3862-72.
Abstract
Melanomas have a high angiogenic potential, but respond poorly to medical treatment and metastasize very early. To understand the early events in tumor angiogenesis, animal models with high tumor resolution and blood vessel resolution are required, which provide the opportunity to test the ability of small molecule inhibitors to modulate the angiogenic tumor program. We have established a transgenic melanoma angiogenesis model in the small laboratory fish species Japanese medaka. Here, pigment cells are transformed by an oncogenic receptor tyrosine kinase in fish expressing GFP throughout their vasculature. We show that angiogenesis occurs in a reactive oxygen species (ROS)- and NF-κB-dependent, but hypoxia-independent manner. Intriguingly, we observed that blood vessel sprouting is induced even by single transformed pigment cells. The oncogenic receptor as well as human melanoma cells harboring other oncogenes caused the production of pro-angiogenic factors, most prominently angiogenin, through NF-κB signaling. Inhibiting NF-κB prevented tumor angiogenesis and led to the regression of existing tumor blood vessels. In conclusion, our high-resolution medaka melanoma model discloses that ROS and NF-κB signaling from single tumor cells causes hypoxia-independent angiogenesis, thus, demonstrating that the intrinsic malignant tumor cell features are sufficient to initiate and maintain a pro-angiogenic signaling threshold.
Bärenz F, Inoue D, Yokoyama H, Tegha-Dunghu J, Freiss S, Draeger S, Mayilo D, Cado I, Merker S, Klinger M, Hoeckendorf B, Pilz S, Hupfeld K, Steinbeisser H, Lorenz H, Ruppert T, Wittbrodt J, Gruss OJ. (2013). The centriolar satellite protein SSX2IP promotes centrosome maturation. J Cell Biol. 202(1):81-95.
Abstract
Meiotic maturation in vertebrate oocytes is an excellent model system for microtubule reorganization during M-phase spindle assembly. Here, we surveyed changes in the pattern of microtubule-interacting proteins upon Xenopus laevis oocyte maturation by quantitative proteomics. We identified the synovial sarcoma X breakpoint protein (SSX2IP) as a novel spindle protein. Using X. laevis egg extracts, we show that SSX2IP accumulated at spindle poles in a Dynein-dependent manner and interacted with the γ-tubulin ring complex (γ-TuRC) and the centriolar satellite protein PCM-1. Immunodepletion of SSX2IP impeded γ-TuRC loading onto centrosomes. This led to reduced microtubule nucleation and spindle assembly failure. In rapidly dividing blastomeres of medaka (Oryzias latipes) and in somatic cells, SSX2IP knockdown caused fragmentation of pericentriolar material and chromosome segregation errors. We characterize SSX2IP as a novel centrosome maturation and maintenance factor that is expressed at the onset of vertebrate development. It preserves centrosome integrity and faithful mitosis during the rapid cleavage division of blastomeres and in somatic cells.
Herder C, Swiercz JM, Müller C, Peravali R, Quiring R, Offermanns S, Wittbrodt J, Loosli F. (2013). ArhGEF18 regulates RhoA-Rock2 signaling to maintain neuro-epithelial apico-basal polarity and proliferation. Development. 140(13):2787-97.
Abstract
The vertebrate central nervous system develops from an epithelium where cells are polarized along the apicobasal axis. Loss of this polarity results in abnormal organ architecture, morphology and proliferation. We found that mutations of the guanine nucleotide exchange factor ArhGEF18 affect apicobasal polarity of the retinal neuroepithelium in medaka fish. We show that ArhGEF18-mediated activation of the small GTPase RhoA is required to maintain apicobasal polarity at the onset of retinal differentiation and to control the ratio of neurogenic to proliferative cell divisions. RhoA signals through Rock2 to regulate apicobasal polarity, tight junction localization and the cortical actin cytoskeleton. The human ArhGEF18 homologue can rescue the mutant phenotype, suggesting a conserved function in vertebrate neuroepithelia. Our analysis identifies ArhGEF18 as a key regulator of tissue architecture and function, controlling apicobasal polarity and proliferation through RhoA activation. We thus identify the control of neuroepithelial apicobasal polarity as a novel role for RhoA signaling in vertebrate development.
Sinn R, Wittbrodt J. (2013). An eye on eye development. Mech Dev. 130(6-8):347-58.
Abstract
The vertebrate eye is composed of both surface ectodermal and neuroectodermal derivatives that evaginate laterally from an epithelial anlage of the forming diencephalon. The retina is composed of a limited number of neuronal and non-neuronal cell types and is seen as a model for the brain with reduced complexity. The eye develops in a stereotypic manner building on evolutionarily conserved molecular networks. Eye formation is initiated at the onset of gastrulation by the determination of the eye field in the anterior neuroectoderm. Homeobox transcription factors, in particular Six3 are crucially involved in the establishment and maintenance of retinal identity. The eye field expands by proliferation as gastrulation proceeds and is initially confined to a single retinal primordium by the differential activity of specifying transcription factors. This central field is subsequently split in response to secreted factors emanating from the ventral midline. Concomitant with medio-lateral patterning at the onset of neurulation, morphogenesis sets in and laterally evaginates the optic vesicle. Strikingly during this process the neuroectoderm in the eye field transiently loses epithelial features and cells migrate individually. In a second morphogenetic event, the vesicle is transformed into the optic cup, concomitant with onset and progression of retinal differentiation. Accompanying optic cup morphogenesis, neural differentiation is initiated from a retinal signalling centre in a stereotypic and species specific manner by secreted signalling factors. Here we will give an overview of key events during vertebrate eye formation and highlight key players in the respective processes.
2012
Höckendorf B, Thumberger T, Wittbrodt J. (2012). Quantitative analysis of embryogenesis: a perspective for light sheet microscopy. Dev Cell. 23(6):1111-20.
Abstract
Alten L, Schuster-Gossler K, Eichenlaub MP, Wittbrodt B, Wittbrodt J, Gossler A. (2012). A novel mammal-specific three partite enhancer element regulates node and notochord-specific Noto expression. PLoS One. 2012;7(10):e47785.
Abstract
Bogdanovic O, Delfino-Machín M, Nicolás-Pérez M, Gavilán MP, Gago-Rodrigues I, Fernández-Miñán A, Lillo C, Ríos RM, Wittbrodt J, Martínez-Morales JR. (2012). Numb/Numbl-Opo antagonism controls retinal epithelium morphogenesis by regulating integrin endocytosis. Dev Cell. 23(4):782-95.
Abstract
ENCODE Project Consortium, Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F, Epstein CB, Frietze S, Harrow J, Kaul R, Khatun J, Lajoie BR, Landt SG, Lee BK, Pauli F, Rosenbloom KR, Sabo P, Safi A, Sanyal A, Shoresh N, Simon JM, Song L, Trinklein ND, Altshuler RC, Birney E, Brown JB, Cheng C, Djebali S, Dong X, Dunham I, Ernst J, Furey TS, Gerstein M, Giardine B, Greven M, Hardison RC, Harris RS, Herrero J, Hoffman MM, Iyer S, Kelllis M, Khatun J, Kheradpour P, Kundaje A, Lassmann T, Li Q, Lin X, Marinov GK, Merkel A, Mortazavi A, Parker SC, Reddy TE, Rozowsky J, Schlesinger F, Thurman RE, Wang J, Ward LD, Whitfield TW, Wilder SP, Wu W, Xi HS, Yip KY, Zhuang J, Bernstein BE, Birney E, Dunham I, Green ED, Gunter C, Snyder M, Pazin MJ, Lowdon RF, Dillon LA, Adams LB, Kelly CJ, Zhang J, Wexler JR, Green ED, Good PJ, Feingold EA, Bernstein BE, Birney E, Crawford GE, Dekker J, Elinitski L, Farnham PJ, Gerstein M, Giddings MC, Gingeras TR, Green ED, Guigó R, Hardison RC, Hubbard TJ, Kellis M, Kent WJ, Lieb JD, Margulies EH, Myers RM, Snyder M, Starnatoyannopoulos JA, Tennebaum SA, Weng Z, White KP, Wold B, Khatun J, Yu Y, Wrobel J, Risk BA, Gunawardena HP, Kuiper HC, Maier CW, Xie L, Chen X, Giddings MC, Bernstein BE, Epstein CB, Shoresh N, Ernst J, Kheradpour P, Mikkelsen TS, Gillespie S, Goren A, Ram O, Zhang X, Wang L, Issner R, Coyne MJ, Durham T, Ku M, Truong T, Ward LD, Altshuler RC, Eaton ML, Kellis M, Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue C, Marinov GK, Khatun J, Williams BA, Zaleski C, Rozowsky J, Röder M, Kokocinski F, Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Batut P, Bell I, Bell K, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T, Drenkow J, Dumais E, Dumais J, Duttagupta R, Fastuca M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood MJ, Gao H, Gonzalez D, Gordon A, Gunawardena HP, Howald C, Jha S, Johnson R, Kapranov P, King B, Kingswood C, Li G, Luo OJ, Park E, Preall JB, Presaud K, Ribeca P, Risk BA, Robyr D, Ruan X, Sammeth M, Sandu KS, Schaeffer L, See LH, Shahab A, Skancke J, Suzuki AM, Takahashi H, Tilgner H, Trout D, Walters N, Wang H, Wrobel J, Yu Y, Hayashizaki Y, Harrow J, Gerstein M, Hubbard TJ, Reymond A, Antonarakis SE, Hannon GJ, Giddings MC, Ruan Y, Wold B, Carninci P, Guigó R, Gingeras TR, Rosenbloom KR, Sloan CA, Learned K, Malladi VS, Wong MC, Barber GP, Cline MS, Dreszer TR, Heitner SG, Karolchik D, Kent WJ, Kirkup VM, Meyer LR, Long JC, Maddren M, Raney BJ, Furey TS, Song L, Grasfeder LL, Giresi PG, Lee BK, Battenhouse A, Sheffield NC, Simon JM, Showers KA, Safi A, London D, Bhinge AA, Shestak C, Schaner MR, Kim SK, Zhang ZZ, Mieczkowski PA, Mieczkowska JO, Liu Z, McDaniell RM, Ni Y, Rashid NU, Kim MJ, Adar S, Zhang Z, Wang T, Winter D, Keefe D, Birney E, Iyer VR, Lieb JD, Crawford GE, Li G, Sandhu KS, Zheng M, Wang P, Luo OJ, Shahab A, Fullwood MJ, Ruan X, Ruan Y, Myers RM, Pauli F, Williams BA, Gertz J, Marinov GK, Reddy TE, Vielmetter J, Partridge EC, Trout D, Varley KE, Gasper C, Bansal A, Pepke S, Jain P, Amrhein H, Bowling KM, Anaya M, Cross MK, King B, Muratet MA, Antoshechkin I, Newberry KM, McCue K, Nesmith AS, Fisher-Aylor KI, Pusey B, DeSalvo G, Parker SL, Balasubramanian S, Davis NS, Meadows SK, Eggleston T, Gunter C, Newberry JS, Levy SE, Absher DM, Mortazavi A, Wong WH, Wold B, Blow MJ, Visel A, Pennachio LA, Elnitski L, Margulies EH, Parker SC, Petrykowska HM, Abyzov A, Aken B, Barrell D, Barson G, Berry A, Bignell A, Boychenko V, Bussotti G, Chrast J, Davidson C, Derrien T, Despacio-Reyes G, Diekhans M, Ezkurdia I, Frankish A, Gilbert J, Gonzalez JM, Griffiths E, Harte R, Hendrix DA, Howald C, Hunt T, Jungreis I, Kay M, Khurana E, Kokocinski F, Leng J, Lin MF, Loveland J, Lu Z, Manthravadi D, Mariotti M, Mudge J, Mukherjee G, Notredame C, Pei B, Rodriguez JM, Saunders G, Sboner A, Searle S, Sisu C, Snow C, Steward C, Tanzer A, Tapanari E, Tress ML, van Baren MJ, Walters N, Washieti S, Wilming L, Zadissa A, Zhengdong Z, Brent M, Haussler D, Kellis M, Valencia A, Gerstein M, Raymond A, Guigó R, Harrow J, Hubbard TJ, Landt SG, Frietze S, Abyzov A, Addleman N, Alexander RP, Auerbach RK, Balasubramanian S, Bettinger K, Bhardwaj N, Boyle AP, Cao AR, Cayting P, Charos A, Cheng Y, Cheng C, Eastman C, Euskirchen G, Fleming JD, Grubert F, Habegger L, Hariharan M, Harmanci A, Iyenger S, Jin VX, Karczewski KJ, Kasowski M, Lacroute P, Lam H, Larnarre-Vincent N, Leng J, Lian J, Lindahl-Allen M, Min R, Miotto B, Monahan H, Moqtaderi Z, Mu XJ, O'Geen H, Ouyang Z, Patacsil D, Pei B, Raha D, Ramirez L, Reed B, Rozowsky J, Sboner A, Shi M, Sisu C, Slifer T, Witt H, Wu L, Xu X, Yan KK, Yang X, Yip KY, Zhang Z, Struhl K, Weissman SM, Gerstein M, Farnham PJ, Snyder M, Tenebaum SA, Penalva LO, Doyle F, Karmakar S, Landt SG, Bhanvadia RR, Choudhury A, Domanus M, Ma L, Moran J, Patacsil D, Slifer T, Victorsen A, Yang X, Snyder M, White KP, Auer T, Centarin L, Eichenlaub M, Gruhl F, Heerman S, Hoeckendorf B, Inoue D, Kellner T, Kirchmaier S, Mueller C, Reinhardt R, Schertel L, Schneider S, Sinn R, Wittbrodt B, Wittbrodt J, Weng Z, Whitfield TW, Wang J, Collins PJ, Aldred SF, Trinklein ND, Partridge EC, Myers RM, Dekker J, Jain G, Lajoie BR, Sanyal A, Balasundaram G, Bates DL, Byron R, Canfield TK, Diegel MJ, Dunn D, Ebersol AK, Ebersol AK, Frum T, Garg K, Gist E, Hansen RS, Boatman L, Haugen E, Humbert R, Jain G, Johnson AK, Johnson EM, Kutyavin TM, Lajoie BR, Lee K, Lotakis D, Maurano MT, Neph SJ, Neri FV, Nguyen ED, Qu H, Reynolds AP, Roach V, Rynes E, Sabo P, Sanchez ME, Sandstrom RS, Sanyal A, Shafer AO, Stergachis AB, Thomas S, Thurman RE, Vernot B, Vierstra J, Vong S, Wang H, Weaver MA, Yan Y, Zhang M, Akey JA, Bender M, Dorschner MO, Groudine M, MacCoss MJ, Navas P, Stamatoyannopoulos G, Kaul R, Dekker J, Stamatoyannopoulos JA, Dunham I, Beal K, Brazma A, Flicek P, Herrero J, Johnson N, Keefe D, Lukk M, Luscombe NM, Sobral D, Vaquerizas JM, Wilder SP, Batzoglou S, Sidow A, Hussami N, Kyriazopoulou-Panagiotopoulou S, Libbrecht MW, Schaub MA, Kundaje A, Hardison RC, Miller W, Giardine B, Harris RS, Wu W, Bickel PJ, Banfai B, Boley NP, Brown JB, Huang H, Li Q, Li JJ, Noble WS, Bilmes JA, Buske OJ, Hoffman MM, Sahu AO, Kharchenko PV, Park PJ, Baker D, Taylor J, Weng Z, Iyer S, Dong X, Greven M, Lin X, Wang J, Xi HS, Zhuang J, Gerstein M, Alexander RP, Balasubramanian S, Cheng C, Harmanci A, Lochovsky L, Min R, Mu XJ, Rozowsky J, Yan KK, Yip KY, Birney E. (2012). An integrated encyclopedia of DNA elements in the human genome. Nature. 489(7414):57-74.
Abstract
Schulz S, Chachami G, Kozaczkiewicz L, Winter U, Stankovic-Valentin N, Haas P, Hofmann K, Urlaub H, Ovaa H, Wittbrodt J, Meulmeester E, Melchior F. (2012). Ubiquitin-specific protease-like 1 (USPL1) is a SUMO isopeptidase with essential, non-catalytic functions. EMBO Rep. 13(10):930-8.
Abstract
Harden MV, Pereiro L, Ramialison M, Wittbrodt J, Prasad MK, McCallion AS, Whitlock KE. (2012). Close association of olfactory placode precursors and cranial neural crest cells does not predestine cell mixing. Dev Dyn. 241(7):1143-54.
Abstract
Ramialison M, Reinhardt R, Henrich T, Wittbrodt B, Kellner T, Lowy CM, Wittbrodt J. (2012). Cis-regulatory properties of medaka synexpression groups. Development. 139(5):917-28.
Abstract
2011
Centanin L, Hoeckendorf B, Wittbrodt J. (2011). Fate restriction and multipotency in retinal stem cells. Cell Stem Cell. 9(6):553-62.
Abstract
Keller PJ, Schmidt AD, Wittbrodt J, Stelzer EH. (2011). Digital scanned laser light-sheet fluorescence microscopy (DSLM) of zebrafish and Drosophila embryonic development. Cold Spring Harb Protoc. 2011(10):1235-43.
Abstract
Mongin E, Auer TO, Bourrat F, Gruhl F, Dewar K, Blanchette M, Wittbrodt J, Ettwiller L. (2011). Combining computational prediction of cis-regulatory elements with a new enhancer assay to efficiently label neuronal structures in the medaka fish. PLoS One. 2011;6(5):e19747.
Abstract
Inoue D, Wittbrodt J. (2011). One for all--a highly efficient and versatile method for fluorescent immunostaining in fish embryos. PLoS One. 2011;6(5):e19713.
Abstract
Maurya AK, Tan H, Souren M, Wang X, Wittbrodt J, Ingham PW. (2011). Integration of Hedgehog and BMP signalling by the engrailed2a gene in the zebrafish myotome. Development. 138(4):755-65.
Abstract
2010
Keller PJ, Schmidt AD, Santella A, Khairy K, Bao Z, Wittbrodt J, Stelzer EH. (2010). Fast, high-contrast imaging of animal development with scanned light sheet-based structured-illumination microscopy. Nat Methods. 7(8):637-42.
Abstract
Haudry Y, Ramialison M, Paten B, Wittbrodt J, Ettwiller L. (2010). Using Trawler_standalone to discover overrepresented motifs in DNA and RNA sequences derived from various experiments including chromatin immunoprecipitation. Nat Protoc. 5(2):323-34.
Abstract
2009
Brown KE, Keller PJ, Ramialison M, Rembold M, Stelzer EH, Loosli F, Wittbrodt J. (2009). Nlcam modulates midline convergence during anterior neural plate morphogenesis. Dev Biol. 339(1):14-25.
Abstract
Martinez-Morales JR, Wittbrodt J. (2009). Shaping the vertebrate eye. Curr Opin Genet Dev. 19(5):511-7.
Abstract
Bajoghli B, Ramialison M, Aghaallaei N, Czerny T, Wittbrodt J. (2009). Identification of starmaker-like in medaka as a putative target gene of Pax2 in the otic vesicle. Dev Dyn.238(11):2860-6.
Abstract
Mertes F, Martinez-Morales JR, Nolden T, Spörle R, Wittbrodt J, Lehrach H, Himmelbauer H. (2009). Cloning of mouse ojoplano, a reticular cytoplasmic protein expressed during embryonic development. Gene Expr Patterns.9(8):562-7.
Abstract
Souren M, Martinez-Morales JR, Makri P, Wittbrodt B, Wittbrodt J. (2009). A global survey identifies novel upstream components of the Ath5 neurogenic network. Genome Biol. 2009;10(9):R92.
Abstract
Martinez-Morales JR, Rembold M, Greger K, Simpson JC, Brown KE, Quiring R, Pepperkok R, Martin-Bermudo MD, Himmelbauer H, Wittbrodt J. (2009). ojoplano-mediated basal constriction is essential for optic cup morphogenesis. Development. 136(13):2165-75.
Abstract
Sano S, Takashima S, Niwa H, Yokoi H, Shimada A, Arenz A, Wittbrodt J, Takeda H. (2009). Characterization of teleost Mdga1 using a gene-trap approach in medaka (Oryzias latipes). Genesis. 47(8):505-13.
Abstract
Signore IA, Guerrero N, Loosli F, Colombo A, Villalón A, Wittbrodt J, Concha ML. (2009). Zebrafish and medaka: model organisms for a comparative developmental approach of brain asymmetry. Philos Trans R Soc Lond B Biol Sci. 364(1519):991-1003.
2008
Ettwiller L, Budd A, Spitz F, Wittbrodt J. (2008). Analysis of mammalian gene batteries reveals both stable ancestral cores and highly dynamic regulatory sequences. Genome Biol. 9(12):R172.
Grabher C, Wittbrodt J.(2008). Recent advances in meganuclease-and transposon-mediated transgenesis of medaka and zebrafish. Methods Mol Biol. 461:521-39.
Abstract
Keller PJ*, Schmidt AD, Wittbrodt J*, Stelzer EH. (2008). Reconstruction of zebrafish early embryonic development by scanned light sheet microscopy. Science. 322(5904):1065-9. * corresponding authors
Abstract
Ramialison M, Bajoghli B, Aghaallaei N, Ettwiller L, Gaudan S, Wittbrodt B, Czerny T, Wittbrodt J. (2008). Rapid identification of PAX2/5/8 direct downstream targets in the otic vesicle by combinatorial use of bioinformatics tools. Genome Biol. 9(10):R145.
Abstract
2007
Grabher C, Wittbrodt J. (2007). Meganuclease and transposon mediated transgenesis in medaka. Genome Biol. 8 Suppl 1:S10.
Abstract
Haudry Y, Berube H, Letunic I, Weeber PD, Gagneur J, Girardot C, Kapushesky M, Arendt D, Bork P, Brazma A, Furlong EE, Wittbrodt J, Henrich T. (2007). 4DXpress: a database for cross-species expression pattern comparisons. Nucleic Acids Res.36(Database issue):D847-53.
Abstract
Del Bene F, Ettwiller L, Skowronska-Krawczyk D, Baier H, Matter JM, Birney E, Wittbrodt J. (2007). In vivo validation of a computationally predicted conserved Ath5 target gene set. PLoS Genet. 3(9):1661-71.
Abstract
Ettwiller L, Paten B, Ramialison M, Birney E, Wittbrodt J. (2007). Trawler: de novo regulatory motif discovery pipeline for chromatin immunoprecipitation. Nat Methods. 4(7):563-5.
Abstract
Rembold M, Lahiri K, Foulkes NS, Wittbrodt J. (2006). Transgenesis in fish: efficient selection of transgenic fish by co-injection with a fluorescent reporter construct. Nat Protoc. 1(3):1133-9.
Abstract
Martinez-Morales JR, Henrich T, Ramialison M, Wittbrodt J. (2007). New genes in the evolution of the neural crest differentiation program. Genome Biol. 8(3):R36.
Abstract
Steinmetz PR, Zelada-Gonzáles F, Burgtorf C, Wittbrodt J, Arendt D. (2007). Polychaete trunk neuroectoderm converges and extends by mediolateral cell intercalation. Proc Natl Acad Sci U S A. 104(8):2727-32.
Abstract
2006
Yokoi H, Shimada A, Carl M, Takashima S, Kobayashi D, Narita T, Jindo T, Kimura T, Kitagawa T, Kage T, Sawada A, Naruse K, Asakawa S, Shimizu N, Mitani H, Shima A, Tsutsumi M, Hori H, Wittbrodt J, Saga Y, Ishikawa Y, Araki K, Takeda H. (2006). Mutant analyses reveal different functions of fgfr1 in medaka and zebrafish despite conserved ligand-receptor relationships. Dev Biol.304(1):326-37.
Abstract
Grabher C, Cliffe A, Miura K, Hayflick J, Pepperkok R, Rørth P, Wittbrodt J. (2007). Birth and life of tissue macrophages and their migration in embryogenesis and inflammation in medaka. J Leukoc Biol.81(1):263-71.
Abstract
Ason B, Darnell DK, Wittbrodt B, Berezikov E, Kloosterman WP, Wittbrodt J, Antin PB, Plasterk RH. (2006). Differences in vertebrate microRNA expression. Proc Natl Acad Sci U S A.103(39):14385-9.
Abstract
Rembold M, Loosli F, Adams RJ, Wittbrodt J. (2006). Individual cell migration serves as the driving force for optic vesicle evagination. Science. 313(5790):1130-4.
Abstract
Swindell EC, Bailey TJ, Loosli F, Liu C, Amaya-Manzanares F, Mahon KA, Wittbrodt J, Jamrich M. (2006). Rx-Cre, a tool for inactivation of gene expression in the developing retina. Genesis.44(8):361-3.
Nakamura S, Kobayashi D, Aoki Y, Yokoi H, Ebe Y, Wittbrodt J, Tanaka M. (2006). Identification and lineage tracing of two populations of somatic gonadal precursors in medaka embryos. Dev Biol.295(2):678-88.
Abstract
publications before 2006
Ettwiller L, Paten B, Souren M, Loosli F, Wittbrodt J, Birney E. (2005). The discovery, positioning and verification of a set of transcription-associated motifs in vertebrates. Genome Biol. 6(12):R104.
Abstract
Wichmann O, Wittbrodt J, Schultz C. (2006). A small-molecule FRET probe to monitor phospholipase A2 activity in cells and organisms. Angew Chem Int Ed Engl.45(3):508-12.
Abstract
Fritzsch B, Piatigorsky J, Tessmar-Raible K, Jékely G, Guy K, Raible F, Wittbrodt J, Arendt D. (2005). Ancestry of Photic and Mechanic Sensation? Science. 308(5725):1113-1114.
Henrich T, Ramialison M, Wittbrodt B, Assouline B, Bourrat F, Berger A, Himmelbauer H, Sasaki T, Shimizu N, Westerfield M, Kondoh H, Wittbrodt J. (2005). MEPD: a resource for medaka gene expression patterns. Bioinformatics.21(14):3195-7.
Abstract
Del Bene F, Wittbrodt J. (2005). Cell cycle control by homeobox genes in development and disease. Semin Cell Dev Biol. 16(3):449-60.
Abstract
Schäfer M, Rembold M, Wittbrodt J, Schartl M, Winkler C. (2005). Medial floor plate formation in zebrafish consists of two phases and requires trunk-derived Midkine-a. Genes Dev. 19(8):897-902.
Abstract
Martinez-Morales JR, Del Bene F, Nica G, Hammerschmidt M, Bovolenta P, Wittbrodt J. (2005). Differentiation of the vertebrate retina is coordinated by an FGF signaling center. Dev Cell. 8(4):565-74.
Abstract







Loosli F(1), Köster RW, Carl M, Kühnlein R, Henrich T, Mücke M, Krone A, Wittbrodt J. (2000). A genetic screen for mutations affecting embryonic development in medaka fish (Oryzias latipes). Mech Dev. 97(1-2):133-9.

Wittbrodt J, Erhardt W. (1989). An inexpensive and versatile computer-controlled PCR machine using a Peltier Element as a thermoelectric heat pump. Trends Genet. 5(7):202-3.