TY - JOUR AB - 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. AU - Dogterom, Marileen AU - Felix, M. AU - Guet, Calin C AU - Leibler, Stanislas ID - 3756 IS - 1 JF - Journal of Cell Biology SN - 0021-9525 TI - Influence of M-phase chromatin on the anisotropy of microtubule asters VL - 133 ER - TY - JOUR AB - 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. AU - Chazelle, Bernard AU - Edelsbrunner, Herbert AU - Guibas, Leonidas AU - Sharir, Micha AU - Stolfi, Jorge ID - 4027 IS - 5 JF - Algorithmica SN - 0178-4617 TI - Lines in space: Combinatorics and algorithms VL - 15 ER - TY - JOUR AB - 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. AU - Edelsbrunner, Herbert AU - Shah, Nimish ID - 4026 IS - 3 JF - Algorithmica SN - 0178-4617 TI - Incremental topological flipping works for regular triangulations VL - 15 ER - TY - GEN AU - Liang, Jie AU - Edelsbrunner, Herbert AU - Subramaniam, Shankar ID - 4030 IS - 2, Part 2 T2 - Fortieth Annual Meeting TI - Effects of molecular shape representations on boundary element method for protein electrostatics computations VL - 70 ER - TY - GEN AU - Liang, Jie AU - Edelsbrunner, Herbert AU - Pamidghantam, Sudhakar AU - Subramaniam, Shankar ID - 4031 IS - 2, Part 2 T2 - Fortieth Annual Meeting TI - Analytical method for molecular shapes: Area, volume, cavities, interface and pockets VL - 70 ER - TY - JOUR AB - 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. AU - Whitfield, Tanya AU - Granato, Michael AU - Van Eeden, Fredericus AU - Schach, Ursula AU - Brand, Michael AU - Furutani Seiki, Makoto AU - Haffter, Pascal AU - Hammerschmidt, Matthias AU - Heisenberg, Carl-Philipp J AU - Jiang, Yunjin AU - Kane, Donald AU - Kelsh, Robert AU - Mullins, Mary AU - Odenthal, Jörg AU - Nüsslein Volhard, Christiane ID - 4142 JF - Development SN - 0950-1991 TI - Mutations affecting development of the zebrafish inner ear and lateral line VL - 123 ER - TY - JOUR AB - 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. AU - Ransom, David AU - Haffter, Pascal AU - Odenthal, Jörg AU - Brownlie, Alison AU - Vogelsang, Elisabeth AU - Kelsh, Robert AU - Brand, Michael AU - Van Eeden, Fredericus AU - Furutani Seiki, Makoto AU - Granato, Michael AU - Hammerschmidt, Matthias AU - Heisenberg, Carl-Philipp J AU - Jiang, Yunjin AU - Kane, Donald AU - Mullins, Mary AU - Nüsslein Volhard, Christiane ID - 4154 IS - 1 JF - Development SN - 0950-1991 TI - Characterization of zebrafish mutants with defects in embryonic hematopoiesis VL - 123 ER - TY - JOUR AB - 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. AU - Piotrowski, Tatjana AU - Schilling, Thomas AU - Brand, Michael AU - Jiang, Yunjin AU - Heisenberg, Carl-Philipp J AU - Beuchle, Dirk AU - Grandel, Heiner AU - Van Eeden, Fredericus AU - Furutani Seiki, Makoto AU - Granato, Michael AU - Haffter, Pascal AU - Hammerschmidt, Matthias AU - Kane, Donald AU - Kelsh, Robert AU - Mullins, Mary AU - Odenthal, Jörg AU - Warga, Rachel AU - Nüsslein Volhard, Christiane ID - 4156 IS - 1 JF - Development SN - 0950-1991 TI - Jaw and branchial arch mutants in zebrafish II: Anterior arches and cartilage differentiation VL - 123 ER - TY - JOUR AB - In a screen for embryonic mutants in the zebrafish a large number of mutants were isolated with abnormal brain morphology, We describe here 26 mutants in 13 complementation groups that show abnormal development of large regions of the brain, Early neurogenesis is affected in white tail (wit), During segmentation stages, homozygous wit embryos display an irregularly formed neural keel, particularly in the hindbrain, Using a variety of molecular markers, a severe increase in the number of various early differentiating neurons can be demonstrated, In contrast, late differentiating neurons, radial glial cells and some nonneural cell types, such as the neural crest-derived melanoblasts, are much reduced, Somitogenesis appears delayed, In addition, very reduced numbers of melanophores are present posterior to the mid-trunk, The wit phenotype is reminiscent of neurogenic mutants in Drosophila, such as Notch or Delta, In mutant parachute (pac) embryos the general organization of the hindbrain is disturbed and many rounded cells accumulate loosely in the hindbrain and midbrain ventricles, Mutants in a group of 6 genes, snakehead(snk), natter (nat), otter (ott) fullbrain (ful) viper (vip) and white snake (wis) develop collapsed brain ventricles, before showing signs of general degeneration, atlantis (atl), big head (bid), wicked brain (win), scabland (sbd) and eisspalte (ele) mutants have different malformation of the brain folds, Some of them have transient phenotypes, and mutant individuals may grow up to adults. AU - Jiang, Yunjin AU - Brand, Michael AU - Heisenberg, Carl-Philipp J AU - Beuchle, Dirk AU - Furutani Seiki, Makoto AU - Kelsh, Robert AU - Warga, Rachel AU - Granato, Michael AU - Haffter, Pascal AU - Hammerschmidt, Matthias AU - Kane, Donald AU - Mullins, Mary AU - Odenthal, Jörg AU - Van Eeden, Fredericus AU - Nüsslein Volhard, Christiane ID - 4191 IS - 1 JF - Development SN - 0950-1991 TI - Mutations affecting neurogenesis and brain morphology in the zebrafish, Danio rerio VL - 123 ER - TY - JOUR AB - Neural crest development involves cell-fate specification, proliferation, patterned cell migration, survival and differentiation, Zebrafish neural crest derivatives include three distinct chromatophores, which are well-suited to genetic analysis of their development, As part of a large-scale mutagenesis screen for embryonic/early larval mutations, we have isolated 285 mutations affecting all aspects of zebrafish larval pigmentation, By complementation analysis, we define 94 genes, We show here that comparison of their phenotypes permits classification of these mutations according to the types of defects they cause, and these suggest which process of neural crest development is probably affected, Mutations in eight genes affect the number of chromatophores: these include strong candidates for genes necessary for the processes of pigment cell specification and proliferation, Mutations in five genes remove part of the wild-type pigment pattern, and suggest a role in larval pigment pattern formation, Mutations in five genes show ectopic chromatophores in distinct sites, and may have implications for chromatophore patterning and proliferation, 76 genes affect pigment or morphology of one or more chromatophore types: these mutations include strong candidates for genes important in various aspects of chromatophore differentiation and survival, In combination with the embryological advantages of zebrafish, these mutations should permit cellular and molecular dissection of many aspects of neural crest development. AU - Kelsh, Robert AU - Brand, Michael AU - Jiang, Yunjin AU - Heisenberg, Carl-Philipp J AU - Lin, Shuo AU - Haffter, Pascal AU - Odenthal, Jörg AU - Mullins, Mary AU - Van Eeden, Fredericus AU - Furutani Seiki, Makoto AU - Granato, Michael AU - Hammerschmidt, Matthias AU - Kane, Donald AU - Warga, Rachel AU - Beuchle, Dirk AU - Vogelsang, Lisa AU - Nüsslein Volhard, Christiane ID - 4186 IS - 1 JF - Development SN - 0950-1991 TI - Zebrafish pigmentation mutations and the processes of neural crest development VL - 123 ER - TY - JOUR AB - This report describes mutants of the zebrafish having phenotypes causing a general arrest in early morphogenesis. These mutants identify a group of loci making up about 20% of the loci identified by mutants with visible morphological phenotypes within the first day of development. There are 12 Class I mutants, which fall into 5 complementation groups and have cells that lyse before morphological defects are observed. Mutants at three loci, speed bump, ogre and zombie, display abnormal nuclei. The 8 Class II mutants, which fall into 6 complementation groups, arrest development before cell lysis is observed. These mutants seemingly stop development in the late segmentation stages, and maintain a body shape similar to a 20 hour embryo. Mutations in speed bump, ogre, zombie, specter, poltergeist and troll were tested for cell lethality by transplanting mutant cells into wild-type hosts. With poltergeist, transplanted mutant cells all survive. The remainder of the mutants tested were autonomously but conditionally lethal: mutant cells, most of which lyse, sometimes survive to become notochord, muscles, or, in rare cases, large neurons, all cell types which become postmitotic in the gastrula. Some of the genes of the early arrest group may be necessary for progression though the cell cycle; if so, the survival of early differentiating cells may be based on having their terminal mitosis before the zygotic requirement for these genes. AU - Kane, Donald AU - Maischein, Hans AU - Brand, Michael AU - Van Eeden, Fredericus AU - Furutani Seiki, Makoto AU - Granato, Michael AU - Haffter, Pascal AU - Hammerschmidt, Matthias AU - Heisenberg, Carl-Philipp J AU - Jiang, Yunjin AU - Kelsh, Robert AU - Mullins, Mary AU - Odenthal, Jörg AU - Warga, Rachel AU - Nüsslein Volhard, Christiane ID - 4189 IS - 1 JF - Development SN - 0950-1991 TI - The zebrafish early arrest mutants VL - 123 ER - TY - JOUR AB - Epiboly, the enveloping of the yolk cell by the blastoderm, is the first zebrafish morphogenetic movement, We isolated four mutations that affect epiboly: half baked, avalanche, lawine and weg, Homozygous mutant embryos arrest the vegetal progress of the deep cells of the blastoderm; only the yolk syncytial layer of the yolk cell and the enveloping layer of the blastoderm reach the vegetal pole of the embryo, The mutations half baked, avalanche and lawine produce a novel dominant effect, termed a zygotic-maternal dominant effect: heterozygous embryos produced from heterozygous females slow down epiboly and accumulate detached cells over the neural tube; a small fraction of these mutant individuals are viable, Heterozygous embryos produced from heterozygous males crossed to homozygous wild-type females complete epiboly normally and are completely viable. Additionally, embryos heterozygous for half baked have an enlarged hatching gland, a partial dominant phenotype, The phenotypes of these mutants demonstrate that, for the spreading of cells during epiboly, the movement of the deep cells of the blastoderm require the function of genes that are not necessary for the movement of the enveloping layer or the yolk cell, Furthermore, the dominant zygotic-maternal effect phenotypes illustrate the maternal and zygotic interplay of genes that orchestrate the early cell movements of the zebrafish. AU - Kane, Donald AU - Hammerschmidt, Matthias AU - Mullins, Mary AU - Maischein, Hans AU - Brand, Michael AU - Van Eeden, Fredericus AU - Furutani Seiki, Makoto AU - Granato, Michael AU - Haffter, Pascal AU - Heisenberg, Carl-Philipp J AU - Jiang, Yunjin AU - Kelsh, Robert AU - Odenthal, Jörg AU - Warga, Rachel AU - Nüsslein Volhard, Christiane ID - 4188 IS - 1 JF - Development SN - 0950-1991 TI - The zebrafish epiboly mutants VL - 123 ER - TY - JOUR AB - We identified four zebrafish mutants with defects in forebrain induction and patterning during embryogenesis. The four mutants define three genes: masterblind (mbl), silverblick (slb), and knollnase (kas), In mbl embryos, the anterior forebrain acquires posterior forebrain characteristics: anterior structures such as the eyes, olfactory placodes and the telencephalon are missing, whereas the epiphysis located in the posterior forebrain is expanded, In slb embryos, the extension of the embryonic axis is initially delayed and eventually followed by a partial fusion of the eyes, Finally, in kas embryos, separation of the telencephalic primordia is incomplete and dorsal midline cells fail to form a differentiated roof plate, Analysis of the mutant phenotypes indicates that we have identified genes essential for the specification of the anterior forebrain (mbl), positioning of the eyes (slb) and differentiation of the roof plate (kas). In an appendix to this study we list mutants showing alterations in the size of the eyes and abnormal differentiation of the lenses. AU - Heisenberg, Carl-Philipp J AU - Brand, Michael AU - Jiang, Yunjin AU - Warga, Rachel AU - Beuchle, Dirk AU - Van Eeden, Fredericus AU - Furutani Seiki, Makoto AU - Granato, Michael AU - Haffter, Pascal AU - Hammerschmidt, Matthias AU - Kane, Donald AU - Kelsh, Robert AU - Mullins, Mary AU - Odenthal, Jörg AU - Nüsslein Volhard, Christiane ID - 4203 JF - Development SN - 0950-1991 TI - Genes involved in forebrain development in the zebrafish, Danio rerio VL - 123 ER - TY - JOUR AB - Tissues of the dorsal midline of vertebrate embryos, such as notochord and floor plate, have been implicated in inductive interactions that pattern the neural tube and somites. In our screen for embryonic visible mutations in the zebrafish we found 113 mutations in more than 27 genes with altered body shape, often with additional defects in CNS development. We concentrated on a subgroup of mutations in ten genes (the midline-group) that cause defective development of the floor plate. By using floor plate markers, such as the signaling molecule sonic hedgehog, we show that the schmalspur (sur) gene is needed for early floor plate development, similar to one-eyed-pinhead (oep) and the previously described cyclops (eye) gene. In contrast to oep and cyc, sur embryos show deletions of ventral CNS tissue restricted to the mid- and hindbrain, whereas the forebrain appears largely unaffected. In the underlying mesendodermal tissue of the head, sur is needed only for development of the posterior prechordal plate, whereas oep and eye are required for both anterior and posterior prechordal plate development. Our analysis of sur mutants suggests that defects within the posterior prechordal plate may cause aberrant development of ventral CNS structures in the mid- and hindbrain. Later development of the floor plate is affected in mutant chameleon, you-too, sonic-you, iguana, detour, schmalkars and monorail embryos; these mutants often show additional defects in tissues that are known to depend on signals from notochord and floor plate, For example, sur, con, and yot mutants show reduction of motor neurons; median deletions of brain tissue are seen in sur, con and yot embryos; and eye, con, yet, igu and dtr mutants often show no or abnormal formation of the optic chiasm. We also find fusions of the ventral neurocranium for all midline mutants tested, which may reveal a hitherto unrecognized function of the midline in influencing differentiation of neural crest cells at their destination. As a working hypothesis, we propose that midline-group genes may act to maintain proper structure and inductive function of zebrafish midline tissues. AU - Brand, Michael AU - Heisenberg, Carl-Philipp J AU - Warga, Rachel AU - Pelegri, Francisco AU - Karlstrom, Rolf AU - Beuchle, Dirk AU - Picker, Alexander AU - Jiang, Yunjin AU - Furutani Seiki, Makoto AU - Van Eeden, Fredericus AU - Granato, Michael AU - Haffter, Pascal AU - Hammerschmidt, Matthias AU - Kane, Donald AU - Kelsh, Robert AU - Mullins, Mary AU - Odenthal, Jörg AU - Nüsslein Volhard, Christiane ID - 4216 IS - 1 JF - Development SN - 0950-1991 TI - Mutations affecting development of the midline and general body shape during zebrafish embryogenesis VL - 123 ER - TY - JOUR AB - Mutations in two genes affect the formation of the boundary between midbrain and hindbrain (MHB): no isthmus (noi) and acerebellar (ace), noi mutant embryos lack the MHB constriction, the cerebellum and optic tectum, as well as the pronephric duct. Analysis of noi mutant embryos with neuron-specific antibodies shows that the MHB region and the dorsal and ventral midbrain are absent or abnormal, but that the rostral hindbrain is unaffected with the exception of the cerebellum, Using markers that are expressed during its formation (eng, wnt1 and pax-b), we find that the MHB region is already misspecified in noi mutant embryos during late gastrulation. The tectum is initially present and later degenerates, The defect in ace mutant embryos is more restricted: MHB and cerebellum are absent, but a tectum is formed, Molecular organisation of the tectum and tegmentum is disturbed, however, since eng, wntl and pax-b marker gene expression is not maintained, We propose that noi and ace are required for development of the MHB region and of the adjacent mid- and hindbrain, which are thought to be patterned by the MHB region, Presence of pax-b RNA, and absence of pax-b protein, together with the observation of genetic linkage and the occurrence of a point mutation, show that noi mutations are located in the pax-b gene, pax-b is a vertebrate orthologue of the Drosophila gene paired, which is involved in a pathway of cellular interactions at the posterior compartment boundary in Drosophila, Our results confirm and extend a previous report, and show that at least one member of this conserved signalling pathway is required for formation of the boundary between midbrain and hindbrain in the zebrafish. AU - Brand, Michael AU - Heisenberg, Carl-Philipp J AU - Jiang, Yunjin AU - Beuchle, Dirk AU - Lun, Klaus AU - Furutani Seiki, Makoto AU - Granato, Michael AU - Haffter, Pascal AU - Hammerschmidt, Matthias AU - Kane, Donald AU - Kelsh, Robert AU - Mullins, Mary AU - Odenthal, Jörg AU - Van Eeden, Fredericus AU - Nüsslein Volhard, Christiane ID - 4219 IS - 1 JF - Development SN - 0950-1991 TI - Mutations in zebrafish genes affecting the formation of the boundary between midbrain and hindbrain VL - 123 ER - TY - JOUR AB - Somitogenesis is the basis of segmentation of the mesoderm in the trunk and tail of vertebrate embryos, Two groups of mutants with defects in this patterning process have been isolated in our screen for zygotic mutations affecting the embryonic development of the zebrafish (Danio rerio), In mutants of the first group, boundaries between individual somites are invisible early on, although the paraxial mesoderm is present, Later, irregular boundaries between somites are present, Mutations infused somites (fss) and beamter (bea) affect all somites, whereas mutations in deadly seven (des), after eight (aei) and white tail (wit) only affect the more posterior somites, Mutants of all genes but wit are homozygous viable and fertile, Skeletal stainings and the expression pattern of myoD and snail1 suggest that anteroposterior patterning within individual somites is abnormal, In the second group of mutants, formation of the horizontal myoseptum, which separates the dorsal and ventral part of the myotome, is reduced, Six genes have been defined in this group (you-type genes), yea-too mutants show the most severe phenotype; in these the adaxial cells, muscle pioneers and the primary motoneurons are affected, in addition to the horizontal myoseptum. The horizontal myoseptum is also missing in mutants that lack a notochord. The similarity of the somite phenotype in mutants lacking the notochord and in the you-type mutants suggests that the genes mutated in these two groups are involved in a signaling pathway from the notochord, important for patterning of the somites. AU - Van Eeden, Fredericus AU - Granato, Michael AU - Schach, Ursula AU - Brand, Michael AU - Furutani Seiki, Makoto AU - Haffter, Pascal AU - Hammerschmidt, Matthias AU - Heisenberg, Carl-Philipp J AU - Jiang, Yunjin AU - Kane, Donald AU - Kelsh, Robert AU - Mullins, Mary AU - Odenthal, Jörg AU - Warga, Rachel AU - Allende, Miguel AU - Weinberg, Eric AU - Nüsslein Volhard, Christiane ID - 4222 IS - 1 JF - Development SN - 0950-1991 TI - Mutations affecting somite formation and patterning in the zebrafish, Danio rerio VL - 123 ER - TY - JOUR AB - In the zebrafish, Danio rerio, a caudal and pectoral fin fold develop during embryogenesis. At larval stages the caudal fin fold is replaced by four different fins, the unpaired anal, dorsal and tail fins. In addition the paired pelvic fins are formed, We have identified a total of 118 mutations affecting larval fin formation, Mutations in 11 genes lead to abnormal morphology or degeneration of both caudal and pectoral fin folds, Most mutants survive to adulthood and form a surprisingly normal complement of adult fins, Mutations in nine genes result in an increased or reduced size of the pectoral fins, Interestingly, in mutants of one of these genes, dackel (dak), pectoral fin buds form initially, but later the fin epithelium fails to expand, Expression of sonic hedgehog mRNA in the posterior mesenchyme of the pectoral fin bud is initiated in dak embryos, but not maintained, Mutations in five other genes affect adult fin but not larval fin development, Two mutants, longfin (lof) and another longfin (alf) have generally longer fins. Stein und bein (sub) has reduced dorsal and pelvic fins, whereas finless (fls) and wanda (wan) mutants affect all adult fins, Finally, mutations in four genes causing defects in embryonic skin formation will be briefly reported. AU - Van Eeden, Fredericus AU - Granato, Michael AU - Schach, Ursula AU - Brand, Michael AU - Furutani Seiki, Makoto AU - Haffter, Pascal AU - Hammerschmidt, Matthias AU - Heisenberg, Carl-Philipp J AU - Jiang, Yunjin AU - Kane, Donald AU - Kelsh, Robert AU - Mullins, Mary AU - Odenthal, Jörg AU - Warga, Rachel AU - Nüsslein Volhard, Christiane ID - 4220 IS - 1 JF - Development SN - 0950-1991 TI - Genetic analysis of fin formation in the zebrafish, Danio rerio VL - 123 ER - TY - CHAP AB - Any sample of genes traces back to a single common ancestor. Each gene also has other properties: its sequence, its geographic location and the phenotype and fitness of the organism that carries it. With sexual reproduction, different genes have different genealogies, which gives us much more information, but also greatly complicates population genetic analysis. We review the close relation between the distribution of genealogies and the classic theory of identity by descent in spatially structured populations, and develop a simple diffusion approximation to the distribution of coalescence times in a homogeneous two-dimensional habitat. This shows that when neighbourhood size is large (as in most populations) only a small fraction of pairs of genes are closely related, and only this fraction gives information about current rates of gene flow. The increase of spatial dispersion with lineage age is thus a poor estimator of gene flow. The bulk of the genealogy depends on the long-term history of the population; we discuss ways of inferring this history from the concordance between genealogies across loci. AU - Barton, Nicholas H AU - Wilson, Ian ID - 4294 SN - 978-0198549840 T2 - New uses for new phylogenies TI - Genealogies and geography ER - TY - CHAP AB - Genetic studies are beginning to provide insights into the evolutionary processes that reduce the fitness of hybrids between recently diverged species. However, the deleterious gene interactions responsible for this fitness reduction are still poorly understood. AU - Barton, Nicholas H ID - 4295 SN - 0960-9822 T2 - Current Biology TI - Speciation: more than the sum of its parts VL - 6 ER - TY - THES AB - A {\em hybrid automaton\/} consists of a finite automaton interacting with a dynamical system. Hybrid automata are used to model embedded controllers and other systems that consist of interacting discrete and continuous components. A hybrid automaton is {\em rectangular\/} if each of its continuous variables~x satisfies a nondeterministic differential equation of the form a≤dxdt≤b, where a and~b are rational constants. Rectangular hybrid automata are particularly useful for the analysis of communication protocols in which local clocks have bounded drift, and for the conservative approximation of systems with more complex continuous behavior. We examine several verification problems on the class of rectangular hybrid automata, including reachability, temporal logic model checking, and controller synthesis. Both dense-time and discrete-time models are considered. We identify subclasses of rectangular hybrid automata for which these problems are decidable and give complexity analyses. An investigation of the structural properties of rectangular hybrid automata is undertaken. One method for proving the decidability of verification problems on infinite-state systems is to find finite quotient systems on which analysis can proceed. Three state-space equivalence relations with strong connections to temporal logic are bisimilarity, similarity, and language equivalence. We characterize the quotient spaces of rectangular hybrid automata with respect to these equivalence relations. AU - Kopke, Peter ID - 4419 TI - The Theory of Rectangular Hybrid Automata ER -