@inproceedings{11910, abstract = {We state a new sampling lemma and use it to improve the running time of dynamic graph algorithms. For the dynamic connectivity problem the previously best randomized algorithm takes expected time O(log3 n) per update, amortized over Ω(m) updates. Using the new sampling lemma, we improve its running time to O(log2 n). There exists a lower bound in the cell probe model for the time per operation of Ω(log n/ log log n) for this problem. Similarly improved running times are achieved for 2-edge connectivity, k-weight minimum spanning tree, and bipartiteness.}, author = {Henzinger, Monika H and Thorup, Mikkel}, booktitle = {23rd International Colloquium on Automata, Languages, and Programming}, isbn = {9783540614401}, issn = {1611-3349}, location = {Paderborn, Germany}, pages = {290--299}, publisher = {Springer Nature}, title = {{Improved sampling with applications to dynamic graph algorithms}}, doi = {10.1007/3-540-61440-0_136}, volume = {1099}, year = {1996}, } @inproceedings{11927, abstract = {We are given a set 7 = {Tl , Tz, . . . , Tk} of rooted binary trees, each Ti leaf-labeled by a subset L(x) c {1,2 )...) n}. IfT is a tree on {1,2, . . , n}, we let T]L denote the subtree of T induced by the nodes of L and all their ancestors. The consensus tree problem asks whether there exists a tree T* such that for every I, T’ IC(Ti) is homeomorphic to Ti. We present algorithms which test if a given set of trees has a consensus tree and if so, construct one. The deterministic algorithm takes time min{O(mn’/‘), O(m + n2 logn)}, where m = Ci IZl and uses linear space. The randomized algorithm takes time O(m log3 n) and uses linear space. The previous best for this problem was an 1981 O(mn) algorithm by Aho et al. Our faster deterministic algorithm uses a new efficient algorithm for the following interesting dynamic graph problem: Given a graph G with n nodes and m edges and a sequence of b batches of one or more edge deletions, then after each batch, either find a new component that has just been created or determine that there is no such component. For this problem, we have a simple algorithm with running time O(n2 log n + be min{ n2, m log n}), where be is the number of batches which do not result in a new component. For our particular application, bc 5 1. If all edges are deleted, then the best previously known deterministic algorithm requires time O(mJ;ii) to solve this problem. computational evolutionary biology. The first application is in the problem of inferring consensus of trees when there can be disagreement[l6]. There have, been several models suggested for this problem[2, 3, 4, 8, ?, 11, 17, 181, of which one is called the Local Consensus Tree[l5]. The local consensus tree model presumes that the user provides a local consensus rule which determines the form of the output tree on (perhaps) each triple of leaves, and the objective is to determine whether a tree exists which is consistent with each of the constraints. We will show that we can construct the local consensus tree of k trees on n species in O(kn3) time, improving on the O(lcn3 + n”) running time if we use the Aho et al algorithm. The second application is a heuristic for constructing the maximum likelihood tree based upon combining solutions to small subproblems. This is a simple and yet potentially significantly interesting approach to the evolutionary tree construction problem. }, author = {Henzinger, Monika H and King, Valerie and Warnow, Tandy}, booktitle = {7th Annual ACM-SIAM Symposium on Discrete Algorithms}, isbn = {0898713668}, location = {Atlanta, GA, United States}, pages = {333 --340}, publisher = {Society for Industrial and Applied Mathematics}, title = {{Constructing a tree from homeomorphic subtrees, with applications to computational evolutionary biology}}, year = {1996}, } @article{3462, author = {Melcher, Thorsten and Geiger, Jörg and Jonas, Peter M and Monyer, Hannah}, issn = {0197-0186}, journal = {Neurochemistry International}, number = {2}, pages = {141 -- 144}, publisher = {Elsevier}, title = {{Analysis of molecular determinants in native AMPA receptors}}, doi = {10.1016/0197-0186(95)00077-1}, volume = {28}, year = {1996}, } @inproceedings{3553, abstract = {Virtual environments open up new opportunities and challenges for geometric modeling systems. A general approach to geometric modeling suitable for the Cave Automatic Virtual Environment is described. The approach is based on alpha complexes, and some of its capabilities are demonstrated by applying it to the study of biomolecules.}, author = {Edelsbrunner, Herbert and Fu, Ping and Quian, Jiang}, booktitle = {Proceedings of the ACM Symposium on Virtual Reality Software and Technology}, isbn = {9780897918251}, location = {Hong Kong}, pages = {35--41 and -- 193--194}, publisher = {ACM}, title = {{Geometric modeling in CAVE}}, doi = {10.1145/3304181.3304190}, year = {1996}, } @article{3634, abstract = {The evolutionary processes responsible for adaptation and speciation on islands differ in several ways from those on the mainland. Most attention has been given to the random genetic drift that arises when a population is founded from just a few colonizing genomes. Theoretical obstacles to 'founder effect speciation' are discussed, together with recent proposals for avoiding them. It is argued that although certain kinds of epistasis can facilitate the evolution of strong reproductive isolation, this favours divergence by selection as much as by random drift.}, author = {Barton, Nicholas H and Mallet, James}, issn = {0962-8436}, journal = {Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences}, number = {1341}, pages = {785 -- 795}, publisher = {Royal Society of London}, title = {{Natural selection and random genetic drift as causes of evolution on islands}}, doi = {10.1098/rstb.1996.0073}, volume = {351}, year = {1996}, } @article{3635, abstract = {Experiments on Drosophila suggest that genetic recombination may result in lowered fitness of progeny (a 'recombination load'). This has been interpreted as evidence either for a direct effect of recombination on fitness, or for the maintenance of linkage disequilibria by epistatic selection. Here we show that such a recombination load is to be expected even if selection favours increased genetic recombination. This is because of the fact that, although a modifier may suffer an immediate loss of fitness if it increases recombination, it eventually becomes associated with a higher additive genetic variance in fitness, which allows a faster response to direction selection. This argument applies to mutation-selection balance with synergistic epistasis, directional selection on quantitative traits, and ectopic exchange among transposable elements. Further experiments are needed to determine whether the selection against recombination due to the immediate load is outweighed by the increased additive variance in fitness produced by recombination.}, author = {Charlesworth, Brian and Barton, Nicholas H}, issn = {0016-6723}, journal = {Genetical Research}, number = {1}, pages = {27 -- 41}, publisher = {Cambridge University Press}, title = {{Recombination load associated with selection for increased recombination}}, doi = {10.1017/S0016672300033450}, volume = {67}, year = {1996}, } @article{3756, abstract = {In many eukaryotic cells going through M-phase, a bipolar spindle is formed by microtubules nucleated from centrosomes. These microtubules, in addition to being `'captured” by kinetochores, may be stabilized by chromatin in two different ways: short-range stabilization effects may affect microtubules in close contact with the chromatin, while long-range stabilization effects may `'guide” microtubule growth towards the chromatin (e.g., by introducing a diffusive gradient of an enzymatic activity that affects microtubule assembly). Here, we use both meiotic and mitotic extracts from Xenopus laevis eggs to study microtubule aster formation and microtubule dynamics in the presence of chromatin. In `'low-speed” meiotic extracts, in the presence of salmon sperm chromatin, we find that short-range stabilization effects lead to a strong anisotropy of the microtubule asters. Analysis of the dynamic parameters of microtubule growth shows that this anisotropy arises from a decrease in the catastrophe frequency, an increase in the rescue frequency and a decrease in the growth velocity. In this system we also find evidence for long-range `'guidance” effects, which lead to a weak anisotropy of the asters. Statistically relevant results on these long-range effects are obtained in `'high-speed” mitotic extracts in the presence of artificially constructed chromatin stripes. We find that aster anisotropy is biased in the direction of the chromatin and that the catastrophe frequency is reduced in its vicinity. In this system we also find a surprising dependence of the catastrophe and the rescue frequencies on the length of microtubules nucleated from centrosomes: the catastrophe frequency increases and the rescue frequency decreases with microtubule length.}, author = {Dogterom, Marileen and Felix, M. and Guet, Calin C and Leibler, Stanislas}, issn = {0021-9525}, journal = {Journal of Cell Biology}, number = {1}, pages = {125 -- 140}, publisher = {Rockefeller University Press}, title = {{Influence of M-phase chromatin on the anisotropy of microtubule asters}}, doi = {doi: 10.1083/jcb.133.1.125 }, volume = {133}, year = {1996}, } @article{4024, abstract = {We have developed general modeling software for a Cave Automatic Virtual Environment (CAVE); one of its applications is modeling 3D protein structures, generating both outside-in and inside-out views of geometric models. An advantage of the CAVE over other virtual environments is that multiple viewers can observe the same scene at the same time and place. Our software is scalable-from high-end virtual environments such as the CAVE, to mid-range immersive desktop systems, down to low-end graphics workstations. In the current configuration, a parallel Silicon Graphics Power Challenge supercomputer architecture performs the computationally intensive construction of surface patches remotely, and sends the results through the I-WAY (Information Wide Area Year) using VBNS (Very-high-Bandwidth Network Systems) to the graphics machines that drive the CAVE and our graphics visualization software, Valvis (Virtual ALpha shapes VISualizer).}, author = {Akkiraju, Nataraj and Edelsbrunner, Herbert and Fu, Ping and Qian, Jiang}, issn = {0018-9162}, journal = {IEEE Computer Graphics and Applications}, number = {4}, pages = {58 -- 61}, publisher = {IEEE}, title = {{Viewing geometric protein structures from inside a CAVE}}, doi = {10.1109/38.511855}, volume = {16}, year = {1996}, } @article{4025, abstract = {Questions of chemical reactivity can often be cast as questions of molecular geometry. Common geometric models for proteins and other molecules are the space-filling diagram, the solvent accessible surface and the molecular surface. In this paper we present a new approach to triangulating the surface of a molecule under the three models, which is fast, robust, and results in topologically correct triangulations. Our computations are based on a simplicial complex dual to the molecule models. All proposed algorithms are parallelizable.}, author = {Akkiraju, Nataraj and Edelsbrunner, Herbert}, issn = {0166-218X}, journal = {Discrete Applied Mathematics}, number = {1-3}, pages = {5 -- 22}, publisher = {Elsevier}, title = {{Triangulating the surface of a molecule}}, doi = {10.1016/S0166-218X(96)00054-6}, volume = {71}, year = {1996}, } @article{4026, abstract = {A set of n weighted points in general position in R(d) defines a unique regular triangulation. This paper proves that if the points are added one by one, then flipping in a topological order will succeed in constructing this triangulation. If, in addition, the points are added in a random sequence and the history of the flips is used for locating the next point, then the algorithm takes expected time at most O(n log n + n(inverted left perpendicular d/2 inverted right perpendicular)). Under the assumption that the points and weights are independently and identically distributed, the expected running time is between proportional to and a factor log n more than the expected size of the regular triangulation. The expectation is over choosing the points and over independent coin-flips performed by the algorithm.}, author = {Edelsbrunner, Herbert and Shah, Nimish}, issn = {0178-4617}, journal = {Algorithmica}, number = {3}, pages = {223 -- 241}, publisher = {Springer}, title = {{Incremental topological flipping works for regular triangulations}}, doi = {10.1007/BF01975867}, volume = {15}, year = {1996}, } @article{4027, abstract = {Questions about lines in space arise frequently as subproblems in three-dimensional computational geometry. In this paper we study a number of fundamental combinatorial and algorithmic problems involving arrangements of n lines in three-dimensional space. Our main results include: 1. A tight Θ(n2) bound on the maximum combinatorial description complexity of the set of all oriented lines that have specified orientations relative to the n given lines. 2. A similar bound of Θ(n3) for the complexity of the set of all lines passing above the n given lines. 3. A preprocessing procedure using O(n2+ε) time and storage, for any ε > 0, that builds a structure supporting O(logn)-time queries for testing if a line lies above all the given lines. 4. An algorithm that tests the "towering property" in O(n4/3+ε) time, for any ε > 0: do n given red lines lie all above n given blue lines? The tools used to obtain these and other results include Plücker coordinates for lines in space and ε-nets for various geometric range spaces.}, author = {Chazelle, Bernard and Edelsbrunner, Herbert and Guibas, Leonidas and Sharir, Micha and Stolfi, Jorge}, issn = {0178-4617}, journal = {Algorithmica}, number = {5}, pages = {428 -- 447}, publisher = {Springer}, title = {{Lines in space: Combinatorics and algorithms}}, doi = {10.1007/BF01955043}, volume = {15}, year = {1996}, } @misc{4030, author = {Liang, Jie and Edelsbrunner, Herbert and Subramaniam, Shankar}, booktitle = {Fortieth Annual Meeting}, number = {2, Part 2}, pages = {A224 -- A224}, publisher = {Cell Press}, title = {{Effects of molecular shape representations on boundary element method for protein electrostatics computations}}, doi = {10.1016/S0006-3495(96)79664-9}, volume = {70}, year = {1996}, } @misc{4031, author = {Liang, Jie and Edelsbrunner, Herbert and Pamidghantam, Sudhakar and Subramaniam, Shankar}, booktitle = {Fortieth Annual Meeting}, number = {2, Part 2}, pages = {A377 -- A377}, publisher = {Cell Press}, title = {{Analytical method for molecular shapes: Area, volume, cavities, interface and pockets}}, doi = {10.1016/S0006-3495(96)79670-4}, volume = {70}, year = {1996}, } @article{4142, abstract = {Mutations giving rise to anatomical defects in the inner ear have been isolated in a large scale screen for mutations causing visible abnormalities in the zebrafish embryo (Haffter, P., Granato, M., Brand, M. et al. (1996) Development 123, 1-36). 58 mutants have been classified as having a primary ear phenotype; these fall into several phenotypic classes, affecting presence or size of the otoliths, size and shape of the otic vesicle and formation of the semicircular canals, and define at least 20 complementation groups. Mutations in seven genes cause loss of one or both otoliths, but do not appear to affect development of other structures within the ear. Mutations in seven genes affect morphology and patterning of the inner ear epithelium, including formation of the semicircular canals and, in some, development of sensory patches (maculae and cristae). Within this class, dog-eared mutants show abnormal development of semicircular canals and lack cristae within the ear, while in van gogh, semicircular canals fail to form altogether, resulting in a tiny otic vesicle containing a single sensory patch. Both these mutants show defects in the expression of homeobox genes within the otic vesicle. In a further class of mutants, ear size is affected while patterning appears to be relatively normal; mutations in three genes cause expansion of the otic vesicle, while in little ears and microtic, the ear is abnormally small, but still contains all five sensory patches, as in the wild type. Many of the ear and otolith mutants show an expected behavioural phenotype: embryos fail to balance correctly, and may swim on their sides, upside down, or in circles. Several mutants with similar balance defects have also been isolated that have no obvious structural ear defect, but that may include mutants with vestibular dysfunction of the inner ear (Granato, M., van Eeden, F. J. M., Schach, U. et al. (1996) Development, 123, 399-413,). Mutations in 19 genes causing primary defects in other structures also show an ear defect. In particular, ear phenotypes are often found in conjunction with defects of neural crest derivatives (pigment cells and/or cartilaginous elements of the jaw). At least one mutant, dog-eared, shows defects in both the ear and another placodally derived sensory system, the lateral line, while hypersensitive mutants have additional trunk lateral line organs.}, author = {Whitfield, Tanya and Granato, Michael and Van Eeden, Fredericus and Schach, Ursula and Brand, Michael and Furutani Seiki, Makoto and Haffter, Pascal and Hammerschmidt, Matthias and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kane, Donald and Kelsh, Robert and Mullins, Mary and Odenthal, Jörg and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, pages = {241 -- 254}, publisher = {Company of Biologists}, title = {{Mutations affecting development of the zebrafish inner ear and lateral line}}, doi = {10.1242/dev.123.1.241}, volume = {123}, year = {1996}, } @article{4151, abstract = {Jaws and branchial arches together are a basic, segmented feature of the vertebrate head, Seven arches develop in the zebrafish embryo (Danio rerio), derived largely from neural crest cells that form the cartilaginous skeleton, In this and the following paper we describe the phenotypes of 109 arch mutants, focusing here on three classes that affect the posterior pharyngeal arches, including the hyoid and five gill-bearing arches, In lockjaw, the hyoid arch is strongly reduced and subsets of branchial arches do not develop, Mutants of a large second class, designated the flathead group, lack several adjacent branchial arches and their associated cartilages. Five alleles at the flathead locus all lead to larvae that lack arches 4-6, Among 34 other flathead group members complementation tests are incomplete, but at least six unique phenotypes can be distinguished, These all delete continuous stretches of adjacent branchial arches and unpaired cartilages in the ventral midline, Many show cell death in the midbrain, from which some neural crest precursors of the arches originate, lockjaw and a few mutants in the flathead group, including pistachio, affect both jaw cartilage and pigmentation, reflecting essential functions of these genes in at least two neural crest lineages, Mutants of a third class, including boxer, dackel and pincher, affect pectoral fins and axonal trajectories in the brain, as well as the arches. Their skeletal phenotypes suggest that they disrupt cartilage morphogenesis in all arches, Our results suggest that there are sets of genes that: (1) specify neural crest cells in groups of adjacent head segments, and (2) function in common genetic pathways in a variety of tissues including the brain, pectoral fins and pigment cells as well as pharyngeal arches.}, author = {Schilling, Thomas and Piotrowski, Tatjana and Grandel, Heiner and Brand, Michael and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Beuchle, Dirk and Hammerschmidt, Matthias and Kane, Donald and Mullins, Mary and Van Eeden, Fredericus and Kelsh, Robert and Furutani Seiki, Makoto and Granato, Michael and Haffter, Pascal and Odenthal, Jörg and Warga, Rachel and Trowe, Torsten and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {329 -- 344}, publisher = {Company of Biologists}, title = {{Jaw and branchial arch mutants in zebrafish I: Branchial arches}}, doi = {10.1242/dev.123.1.329}, volume = {123}, year = {1996}, } @article{4154, abstract = {As part of a large scale chemical mutagenesis screen of the zebrafish (Danio rerio) genome, we have identified 33 mutants with defects in hematopoiesis, Complementation analysis placed 32 of these mutants into 17 complementation groups, The allelism of the remaining 1 blood mutant is currently unresolved, We have categorized these blood mutants into four phenotypic classes based on analyses of whole embryos and isolated blood cells, as well as by in situ hybridization using the hematopoietic transcription factors GATA-1 and GATA-2, Embryos mutant for the gene moonshine have few if any proerythroblasts visible on the day circulation begins and normal erythroid cell differentiation is blocked as determined by staining for hemoglobin and GATA-1 expression, Mutations in five genes, chablis, frascati, merlot, retsina, thunderbird and two possibly unique mutations cause a progressive decrease in the number of blood cells during the first 5 days of development, Mutations in another seven genes, chardonnay, chianti, grenache, sauternes, weibherbst and zinfandel, and two additional mutations result in hypochromic blood cells which also decrease in number as development proceeds, Several of these mutants have immature cells in the circulation, indicating a block in normal erythroid development. The mutation in zinfandel is dominant, and 2-day old heterozygous carriers fail to express detectable levels of hemoglobin and have decreasing numbers of circulating cells during the first 5 days of development, Mutations in two genes, freixenet and yquem, result in the animals that are photosensitive with autofluorescent blood, similar to that found in the human congenital porphyrias, The collection of mutants presented here represent several steps required for normal erythropoiesis, The analysis of these mutants provides a powerful approach towards defining the molecular mechanisms involved in vertebrate hematopoietic development.}, author = {Ransom, David and Haffter, Pascal and Odenthal, Jörg and Brownlie, Alison and Vogelsang, Elisabeth and Kelsh, Robert and Brand, Michael and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Hammerschmidt, Matthias and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kane, Donald and Mullins, Mary and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {311 -- 319}, publisher = {Company of Biologists}, title = {{Characterization of zebrafish mutants with defects in embryonic hematopoiesis}}, doi = {10.1242/dev.123.1.311}, volume = {123}, year = {1996}, } @article{4156, abstract = {In a large scale screen for mutants that affect the early development of the zebrafish, 109 mutants were found that cause defects in the formation of the jaw and the more posterior pharyngeal arches, Here we present the phenotypic description and results of the complementation analysis of mutants belonging to two major classes: (1) mutants with defects in the mandibular and hyoid arches and (2) mutants with defects in cartilage differentiation and growth in all arches, Mutations in four of the genes identified during the screen show specific defects in the first two arches and leave the more posterior pharyngeal arches largely unaffected (schmerle, sucker, hoover and sturgeon). In these mutants ventral components of the mandibular and hyoid arches are reduced (Meckel's cartilage and ceratohyal cartilage) whereas dorsal structures (palato-quadrate and hyosymplectic cartilages) are of normal size or enlarged, Thus, mutations in single genes cause defects in the formation of first and second arch structures but also differentially affect development of the dorsal and ventral structures within one arch. In 27 mutants that define at least 8 genes, the differentiation of cartilage and growth is affected. In hammerhead mutants particularly the mesodermally derived cartilages are reduced, whereas jellyfish mutant larvae are characterized by a severe reduction of all cartilaginous elements, leaving only two pieces in the position of the ceratohyal cartilages. In all other mutant larvae all skeletal elements are present, but consist of smaller and disorganized chondrocytes. These mutants also exhibit shortened heads and reduced pectoral fins. In homozygous knorrig embryos, tumor-like outgrowths of chondrocytes occur along the edges of all cartilaginous elements. The mutants presented here may be valuable tools for elucidating the genetic mechanisms that underlie the development of the mandibular and the hyoid arches, as well as the process of cartilage differentiation.}, author = {Piotrowski, Tatjana and Schilling, Thomas and Brand, Michael and Jiang, Yunjin and Heisenberg, Carl-Philipp J and Beuchle, Dirk and Grandel, Heiner and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Haffter, Pascal and Hammerschmidt, Matthias and Kane, Donald and Kelsh, Robert and Mullins, Mary and Odenthal, Jörg and Warga, Rachel and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {345 -- 356}, publisher = {Company of Biologists}, title = {{Jaw and branchial arch mutants in zebrafish II: Anterior arches and cartilage differentiation}}, doi = {10.1242/dev.123.1.345}, volume = {123}, year = {1996}, } @article{4164, abstract = {In a large-scale screen for mutants with defects in embryonic development we identified 17 genes (65 mutants) specifically required for the development of xanthophores, We provide evidence that these genes are required for three different aspects of xanthophore development, (1) Pigment cell formation and migration (pfeffer and salt); (2) pigment synthesis (edison, yobo, yocca and brie) and (3) pigment translocation (esrom, tilsit and tofu). The number of xanthophore cells that appear in the body is reduced in embryos with mutations in the two genes, salt and pfeffer. In heterozygous and homozygous salt and pfeffer adults, the melanophore stripes are interrupted, indicating that xanthophore cells have an important function in adult melanophore pattern formation, Most other genes affect only larval pigmentation, In embryos mutant for edison, yobo, yocca and brie, differences in pteridine synthesis can be observed under UV light and by thin-layer chromatography. Homozygous mutant females of yobo show a recessive maternal effect, Embryonic development is slowed down and embryos display head and tail truncations, Xanthophores in larvae mutant in the three genes esrom, tilsit and tofu appear less spread out, In addition, these mutants display a defect in retinotectal axon pathfinding, These mutations may affect xanthophore pigment distribution within the cells or xanthophore cell shape, Mutations in seven genes affecting xanthophore pigmentation remain unclassified.}, author = {Odenthal, Jörg and Rossnagel, Karin and Haffter, Pascal and Kelsh, Robert and Vogelsang, Elisabeth and Brand, Michael and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Hammerschmidt, Matthias and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kane, Donald and Mullins, Mary and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {391 -- 398}, publisher = {Company of Biologists}, title = {{Mutations affecting xanthophore pigmentation in the zebrafish, Danio rerio}}, doi = {10.1242/dev.123.1.391}, volume = {123}, year = {1996}, } @article{4166, abstract = {In a large scale screen for mutants with defects in the embryonic development of the zebrafish we identified mutations in four genes, floating head (flh), memo (mom), no tail (ntl), and dec, that are required for early notochord formation. Mutations in flh and ntl have been described previously, while mom and doe are newly identified genes. Mutant mom embryos lack a notochord in the trunk, and trunk somites from the right and left side of the embryo fuse underneath the neural tube. In this respect morn appears similar to flh. In contrast, notochord precursor cells are present in both ntl and doc embryos. In order to gain a greater understanding of the phenotypes, we have analysed the expression of several axial mesoderm markers in mutant embryos of all four genes. In flh and mom, Ntl expression is normal in the germ ring and tailbud, while the expression of Nd and other notochord markers in the axial mesodermal region is disrupted. Nd expression is normal in doc embryos until early semitic stages, when there is a reduction in expression which is first seen in anterior regions of the embryo. This suggests a function for doc in the maintenance of ntl expression. Other notochord markers such as twist, sonic hedgehog and axial are not expressed in the axial mesoderm of ntl embryos, their expression parallels the expression of ntl in the axial mesoderm of mutant doc,flh and mom embryos, indicating that ntl is required for the expression of these markers. The role of doc in the expression of the notochord markers appears indirect via ntl. Floor plate formation is disrupted in most regions in flh and mom mutant embryos but is present in mutant ntl and doc embryos. In mutant embryos with strong ntl alleles the band of cells expressing floor plate markers is broadened. A similar broadening is also observed in the axial mesoderm underlying the floor plate of ntl embryos, suggesting a direct involvement of the notochord precursor cells in floor plate induction. Mutations in al of these four genes result in embryos lacking a horizontal myoseptum and muscle pioneer cells, both of which are thought to be induced by the notochord. These somite defects can be traced back to an impairment of the specification of the adaxial cells during early stages of development. Transplantation of wild-type cells into mutant doc embryos reveals that wild-type notochord cells are sufficient to induce horizontal myoseptum formation in the flanking mutant tissue. Thus dec, like flh and ntl, acts cell autonomously in the notochord. In addition to the four mutants with defects in early notochord formation, we have isolated 84 mutants, defining at least 15 genes, with defects in later stages of notochord development. These are listed in an appendix to this study.}, author = {Odenthal, Jörg and Haffter, Pascal and Vogelsang, Elisabeth and Brand, Michael and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Hammerschmidt, Matthias and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kane, Donald and Kelsh, Robert and Mullins, Mary and Warga, Rachel and Allende, Miguel and Weinberg, Eric and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {103 -- 115}, publisher = {Company of Biologists}, title = {{Mutations affecting the formation of the notochord in the zebrafish, Danio rerio}}, doi = {10.1242/dev.123.1.103}, volume = {123}, year = {1996}, } @article{4170, abstract = {We identified 6 genes that are essential for specifying ventral regions of the early zebrafish embryo, Mutations in these genes cause an expansion of structures normally derived from dorsal-lateral regions of the blastula at the expense of ventrally derived structures, A series of phenotypes of varied strengths is observed with different alleles of these mutants, The weakest phenotype is a reduction in the ventral tail fin, observed as a dominant phenotype of swirl, piggytail, and somitabun and a recessive phenotype of min fin, lost-a-fin and some piggytail alleles, With increasing phenotypic strength, the blood and pronephric anlagen are also reduced or absent, while the paraxial mesoderm and anterior neuroectoderm is progressively expanded, In the strong phenotypes, displayed by homozygous embryos of snailhouse, swirl and somitabun, the somites circle around the embryo and the midbrain region is expanded laterally, Several mutations in this group of genes are semidominant as well as recessive indicating a strong dosage sensitivity of the processes involved, Mutations in the piggytail gene display an unusual dominance that depends on both a maternal and zygotic heterozygous genotype, while somitabun is a fully penetrant dominant maternal-effect mutation, The similar and overlapping phenotypes of mutants of the 6 genes identified suggest that they function in a common pathway, which begins in oogenesis, but also depends on factors provided after the onset of zygotic transcription, presumably during blastula stages, This pathway provides ventral positional information, counteracting the dorsalizing instructions of the organizer, which is localized in the dorsal shield.}, author = {Mullins, Mary and Hammerschmidt, Matthias and Kane, Donald and Odenthal, Jörg and Brand, Michael and Van Eeden, Fredericus and Furutani Seiki, Makoto and Granato, Michael and Haffter, Pascal and Heisenberg, Carl-Philipp J and Jiang, Yunjin and Kelsh, Robert and Nüsslein Volhard, Christiane}, issn = {0950-1991}, journal = {Development}, number = {1}, pages = {81 -- 93}, publisher = {Company of Biologists}, title = {{Genes establishing dorsoventral pattern formation in the zebrafish embryo: The ventral specifying genes}}, doi = {10.1242/dev.123.1.81}, volume = {123}, year = {1996}, }