ZFIN ID: ZDB-PERS-971209-65
Maischein, Hans-Martin
Email: hans.maischein@tuebingen.mpg.de
Address: Department 3 - Genetics Max-Planck-Institut für Entwicklungsbiologie Spemannstrasse 35 Tübingen, D-72076 Germany
Phone: 49-7071-601446
Fax: 49-7071-601384

The earliest patterning events in vertebrate embryogenesis are still poorly understood. In lower vertebrates, these events are initiated by maternal factors present in the egg (such as involved in bicoid localization in Drosophila). In order to identify genes coding for such factors, we are carrying out a screen for maternal-effect mutations in the zebrafish. Mutations are induced in the germ line of parental (P) males by exposing them to the point-mutagen N-ethyl-N-nitroso-urea (ENU). P males are then mated to produce F1 progeny heterozygous for the induced mutations. Eggs are stripped from the F1 females and gynogenesis is artificially induced using early pressure, which inhibits the second meiotic division of the egg. This allows mutations to become homozygous in the gynogenetic F2 generation. Finally, F2 adult females are screened for maternal-effects by crossing them to wild type males and testing their progeny for embryonic phenotypes.

In a pilot screen we raised 204 gynogenetic clutches to adulthood. This led to the identification of one maternal effect mutation. Females homozygous for this mutation are 100% sterile and the embryonic phenotype is independent of the paternal genotype. The mutant embryos can be distinguished as early as the one-cell stage by an increased turbidity in the cytoplasm. We are currently carrying out a larger scale maternal-effect screen in which we planto produce over 1200 gynogenetic adult clutches and screen over 350 genomes. The efficiency of this screen is improved about threefold compared to our pilot screen due the use of lines selected for a more favorable sex ratio under gynogenetic conditions.

In our gynogenetic clutches we also find mutations affecting adult pigmentation and body shape (4 of each type were found in our pilot screen). Thus the use of gynogenesis is useful to identify not only maternal-effect genes, but also genes involved in juvenile and adult traits. Our current screen attempts to combine screens for visual function and adult behavior (H. Baier), skeletal defects (H. Grandel) and fin development and regeneration.

One maternal gene was identified by its zygotic phenotype, unpigmented larval xanthophores. Homozygous yobo females produce embryos which display a number of general defects irrespective of the paternal genotype (Odenthal et al., 1996a).

Jiang, Z., El-Brolosy, M.A., Serobyan, V., Welker, J.M., Retzer, N., Dooley, C.M., Jakutis, G., Juan, T., Fukuda, N., Maischein, H.M., Balciunas, D., Stainier, D.Y.R. (2022) Parental mutations influence wild-type offspring via transcriptional adaptation. Science advances. 8:eabj2029eabj2029
Yang, Y.H.C., Briant, L.J.B., Raab, C.A., Mullapudi, S.T., Maischein, H.M., Kawakami, K., Stainier, D.Y.R. (2022) Innervation modulates the functional connectivity between pancreatic endocrine cells. eLIFE. 11:
Gentile, A., Bensimon-Brito, A., Priya, R., Maischein, H.M., Piesker, J., Guenther, S., Gunawan, F., Stainier, D.Y. (2021) The EMT transcription factor Snai1 maintains myocardial wall integrity by repressing intermediate filament gene expression. eLIFE. 10:
Priya, R., Allanki, S., Gentile, A., Mansingh, S., Uribe, V., Maischein, H.M., Stainier, D.Y.R. (2020) Tension heterogeneity directs form and fate to pattern the myocardial wall. Nature. 588(7836):130-134
Helker, C.S., Eberlein, J., Wilhelm, K., Sugino, T., Malchow, J., Schuermann, A., Baumeister, S., Kwon, H.B., Maischein, H.M., Potente, M., Herzog, W., Stainier, D.Y. (2020) Apelin signaling drives vascular endothelial cells towards a pro-angiogenic state. eLIFE. 9:e55589
Villasenor, A., Gauvrit, S., Collins, M.M., Maischein, H.M., Stainier, D.Y.R. (2019) Hhex regulates the specification and growth of the hepatopancreatic ductal system. Developmental Biology. 458(2):228-236
Fukuda, R., Gunawan, F., Ramadass, R., Beisaw, A., Konzer, A., Mullapudi, S.T., Gentile, A., Maischein, H.M., Graumann, J., Stainier, D.Y.R. (2019) Mechanical Forces Regulate Cardiomyocyte Myofilament Maturation via the VCL-SSH1-CFL Axis. Developmental Cell. 51(1):62-77.e5
Rasouli, S.J., El-Brolosy, M., Tsedeke, A.T., Bensimon-Brito, A., Ghanbari, P., Maischein, H.M., Kuenne, C., Stainier, D.Y. (2018) The flow responsive transcription factor Klf2 is required for myocardial wall integrity by modulating Fgf signaling. eLIFE. 7:
Mullapudi, S.T., Helker, C.S., Boezio, G.L., Maischein, H.M., Sokol, A.M., Guenther, S., Matsuda, H., Kubicek, S., Graumann, J., Yang, Y.H.C., Stainier, D.Y. (2018) Screening for insulin-independent pathways that modulate glucose homeostasis identifies androgen receptor antagonists. eLIFE. 7:
Gauvrit, S., Villasenor, A., Strilic, B., Kitchen, P., Collins, M.M., Marín-Juez, R., Guenther, S., Maischein, H.M., Fukuda, N., Canham, M.A., Brickman, J.M., Bogue, C.W., Jayaraman, P.S., Stainier, D.Y.R. (2018) HHEX is a transcriptional regulator of the VEGFC/FLT4/PROX1 signaling axis during vascular development. Nature communications. 9:2704
Collins, M.M., Maischein, H.M., Dufourcq, P., Charpentier, M., Blader, P., Stainier, D.Y. (2018) Pitx2c orchestrates embryonic axis extension via mesendodermal cell migration. eLIFE. 7:
Lai, J.K.H., Collins, M.M., Uribe, V., Jiménez-Amilburu, V., Günther, S., Maischein, H.M., Stainier, D.Y.R. (2018) The Hippo pathway effector Wwtr1 regulates cardiac wall maturation in zebrafish. Development (Cambridge, England). 145(10)
Eskova, A., Chauvigné, F., Maischein, H.M., Ammelburg, M., Cerdà, J., Nüsslein-Volhard, C., Irion, U. (2017) Gain-of-function mutations of mau/DrAqp3a influence zebrafish pigment pattern formation through the tissue environment. Development (Cambridge, England). 144(11):2059-2069
Gerri, C., Marín-Juez, R., Marass, M., Marks, A., Maischein, H.M., Stainier, D.Y.R. (2017) Hif-1α regulates macrophage-endothelial interactions during blood vessel development in zebrafish. Nature communications. 8:15492
Fukuda, R., Gunawan, F., Beisaw, A., Jimenez-Amilburu, V., Maischein, H.M., Kostin, S., Kawakami, K., Stainier, D.Y. (2017) Proteolysis regulates cardiomyocyte maturation and tissue integration. Nature communications. 8:14495
Matsuoka, R.L., Marass, M., Avdesh, A., Helker, C.S., Maischein, H.M., Grosse, A.S., Kaur, H., Lawson, N.D., Herzog, W., Stainier, D.Y. (2016) Radial glia regulate vascular patterning around the developing spinal cord. eLIFE. 5
Cherian, A.V., Fukuda, R., Augustine, S.M., Maischein, H.M., Stainier, D.Y. (2016) N-cadherin relocalization during cardiac trabeculation. Proceedings of the National Academy of Sciences of the United States of America. 113(27):7569-74
Frohnhöfer, H.G., Geiger-Rudolph, S., Pattky, M., Meixner, M., Huhn, C., Maischein, H.M., Geisler, R., Gehring, I., Maderspacher, F., Nüsslein-Volhard, C., Irion, U. (2016) Spermidine, but not spermine, is essential for pigment pattern formation in zebrafish. Biology Open. 5(6):736-44
Kwon, H.B., Wang, S., Helker, C.S., Rasouli, S.J., Maischein, H.M., Offermanns, S., Herzog, W., Stainier, D.Y. (2016) In vivo modulation of endothelial polarization by Apelin receptor signalling. Nature communications. 7:11805
Panza, P., Sitko, A.A., Maischein, H.M., Koch, I., Flötenmeyer, M., Wright, G.J., Mandai, K., Mason, C.A., Söllner, C. (2015) The LRR receptor Islr2 is required for retinal axon routing at the vertebrate optic chiasm. Neural Development. 10:23
Gao, X., Metzger, U., Panza, P., Mahalwar, P., Alsheimer, S., Geiger, H., Maischein, H.M., Levesque, M.P., Templin, M., Söllner, C. (2015) A Floor-Plate Extracellular Protein-Protein Interaction Screen Identifies Draxin as a Secreted Netrin-1 Antagonist. Cell Reports. 12(4):694-708
Irion, U., Frohnhöfer, H.G., Krauss, J., Çolak Champollion, T., Maischein, H., Geiger-Rudolph, S., Weiler, C., Nüsslein-Volhard, C. (2014) Gap junctions composed of connexions 41.8 and 39.4 are essential for colour pattern formation in zebrafish. eLIFE. 4:1225-38
Krauss, J., Frohnhöfer, H.G., Walderich, B., Maischein, H.M., Weiler, C., Irion, U., Nüsslein-Volhard, C. (2014) Endothelin signalling in iridophore development and stripe pattern formation of zebrafish. Biology Open. 3(6):503-9
Frohnhöfer, H.G., Krauss, J., Maischein, H.M., and Nüsslein-Volhard, C. (2013) Iridophores and their interactions with other chromatophores are required for stripe formation in zebrafish. Development (Cambridge, England). 140(14):2997-3007
Schorpp, M., Bialecki, M., Diekhoff, D., Walderich, B., Odenthal, J., Maischein, H.M., Zapata, A.G., and Boehm, T. (2006) Conserved functions of ikaros in vertebrate lymphocyte development: genetic evidence for distinct larval and adult phases of T cell development and two lineages of B cells in zebrafish. Journal of immunology (Baltimore, Md. : 1950). 177(4):2463-2476
Sonawane, M., Carpio, Y., Geisler, R., Schwarz, H., Maischein, H.M., and Nuesslein-Volhard, C. (2005) Zebrafish penner/lethal giant larvae 2 functions in hemidesmosome formation, maintenance of cellular morphology and growth regulation in the developing basal epidermis. Development (Cambridge, England). 132(14):3255-3265
Pelegri, F., Dekens, M.P., Schulte-Merker, S., Maischein, H.M., Weiler, C., and Nüsslein-Volhard, C. (2004) Identification of recessive maternal-effect mutations in the zebrafish using a gynogenesis-based method. Developmental Dynamics : an official publication of the American Association of Anatomists. 231(2):324-335
Herzog, W., Sonntag, C., Walderich, B., Odenthal, J., Maischein, H.M., and Hammerschmidt, M. (2004) Genetic analysis of adenohypophysis formation in zebrafish. Molecular endocrinology (Baltimore, Md.). 18(5):1185-1195
Gilmour, D., Knaut, H., Maischein, H.M., and Nüsslein-Volhard, C. (2004) Towing of sensory axons by their migrating target cells in vivo. Nature Neuroscience. 7(5):491-492
Dekens, M.P., Pelegri, F.J., Maischein, H.M., and Nüsslein-Volhard, C. (2003) The maternal-effect gene futile cycle is essential for pronuclear congression and mitotic spindle assembly in the zebrafish zygote. Development (Cambridge, England). 130(17):3907-3916
Habeck, H., Odenthal, J., Walderich, B., Maischein, H.-M., Tübingen 2000 screen consortium, and Schulte-Merker, S. (2002) Analysis of a zebrafish VEGF receptor mutant reveals specific disruption of angiogenesis. Current biology : CB. 12(16):1405-1412
Gilmour, D.T., Maischein, H.M., Nüsslein-Volhard, C. (2002) Migration and function of a glial subtype in the vertebrate peripheral nervous system. Neuron. 34(4):577-588
Davidson, A.J., Dooley, K., Schmidt, B., Paffett-Lugassy, N., White, N., Walderich, B., Odenthal, J., Maischein, H.M., Schulte-Merker, S., Nüsslein-Volhard, C., Thisse, C., Thisse, B., and Zon, L.I. (2001) Functional genomics and mutagenesis screening in the zebrafish identifies genes required for hematopoietic stem cell development. Blood. 98(11):1888
Pelegri, F., Knaut, H., Maischein, H.M., Schulte-Merker, S., and Nüsslein-Volhard, C. (1999) A mutation in the zebrafish maternal-effect gene nebel affects furrow formation and vasa RNA localization. Current biology : CB. 9(24):1431-1440
Pelegri, F. and Maischein, H.M. (1998) Function of zebrafish ß-catenin and TCF-3 in dorsoventral patterning. Mechanisms of Development. 77:63-74
Kane, D.A., Hammerschmidt, M., Mullins, M.C., Maischein, H.M., Brand, M., van Eeden, F.J., Furutani-Seiki, M., Granato, M., Haffter, P., Heisenberg, C.P., Jiang, Y.J., Kelsh, R.N., Odenthal, J., Warga, R.M., and Nüsslein-Volhard, C. (1996) The zebrafish epiboly mutants. Development (Cambridge, England). 123:47-55
Kane, D.A., Maischein, H.M., Brand, M., van Eeden, F.J., Furutani-Seiki, M., Granato, M., Haffter, P., Hammerschmidt, M., Heisenberg-, C.P., Jiang, Y.J., Kelsh, R.N., Mullins, M.C., Odenthal, J., Warga, R.M., and Nüsslein-Volhard, C. (1996) The zebrafish early arrest mutants. Development (Cambridge, England). 123:57-66