bluuebunny/crossref_metadata_2025_split huggingface dataset:
Runx3 is required for hematopoietic development in zebrafish
Authors: Kalev‐Zylinska Maggie L. , Horsfield Julia A. , Flores Maria Vega C. , Postlethwait John H. , Chau Jackie Y.M. , Cattin Peter M. , Vitas Maria R. , Crosier Philip S. , Crosier Kathryn E. 
Published: October 2003

AbstractWe cloned zebrafish runx3/aml2/cbfa3 and examined its expression and function during embryogenesis. In the developing embryo, runx3 is dynamically expressed in hematopoietic, neuronal, and cartilaginous tissues. Hematopoietic expression of runx3 commences late in embryogenesis in the ventral tail intermediate cell mass and later colocalizes with spi1 and lyz in circulating blood cells. In the cloche mutant, hematopoietic expression was absent, suggesting that Runx3 functions downstream of cloche in a hematopoietic pathway. Neuronal tissues expressing runx3 include the trigeminal ganglia and Rohon‐Beard neurons. Runx3 appears to contribute to normal development of primitive and definitive hematopoietic cells. When Runx3 function was compromised using morpholino oligonucleotides, a reduction in the number of mature blood cells was observed. Furthermore, Runx3 depletion decreased runx1 expression in the ventral wall of the dorsal aorta and reduced the number of spi1‐ and lyz‐containing blood cells. Conversely, ubiquitous overexpression of runx3 led to an increase in primitive blood cell numbers, together with an increase in runx1‐expressing cells in the ventral wall of the dorsal aorta. We propose a role for Runx3 in the regulation of blood cell numbers. Developmental Dynamics, 2003. © 2003 Wiley‐Liss, Inc.
Functional genomic dissection of multimeric protein families in zebrafish
Authors: Cheng Keith C. , Levenson Robert , Robishaw Janet D. 
Published: October 2003

AbstractThe study of multimeric protein function in the postgenomicera has become complicated by the discovery of multiple isoforms for each subunit of those proteins. A correspondingly large number of potential isoform combinations offer the multicellular organism a constellation of protein assemblies from which to generate a variety of functions across different cells, tissues, and organs. At the same time, the multiplicity of potential subunit isoform combinations presents a significant challenge when attempting to dissect the functions of particular isoform combinations. Biochemical and cell culture methods have brought us to a significant state of understanding of multimeric proteins but are unable to answer questions of function within the context of the many tissues and developmental stages of the multicellular organism. Answering those questions can be greatly facilitated in model systems in which expression can be determined over time, in the context of the whole organism, and in which hypomorphic function of each subunit can be studied individually and in combination. Fortunately, the potential for high‐throughput in situ hybridization studies and antisense‐based reverse genetic knockdowns in zebrafish offers exciting opportunities to meet this challenge. Some of these opportunities, along with cautions of interpretation and gaps in the existing technologies, are discussed in the context of ongoing investigations of the dimeric Na,K‐ATPases and heterotrimeric G proteins. Development Dynamics, 2003. © 2003 Wiley‐Liss, Inc.
Maternal factors in zebrafish development
Authors: Pelegri Francisco 
Published: October 2003

AbstractAll processes that occur before the activation of the zygotic genome at the midblastula transition are driven by maternal products, which are produced during oogenesis and stored in the mature oocyte. Upon egg activation and fertilization, these maternal factors initiate developmental cascades that carry out the embryonic developmental program. Even after the initiation of zygotic gene expression, perduring maternal products continue performing essential functions, either together with other maternal factors or through interactions with newly expressed zygotic products. Advances in zebrafish research have placed this organism in a unique position to contribute to a detailed understanding of the role of maternal factors in early vertebrate development. This review summarizes our knowledge on the processes involved in the production and redistribution of maternal factors during zebrafish oogenesis and early development, as well as our understanding of the function of these factors in axis formation, germ layer and germ cell specification, and other early embryonic processes. Developmental Dynamics, 2003. © 2003 Wiley‐Liss, Inc.
Transgene driving GFP expression from the promoter of the zona pellucida gene zpc is expressed in oocytes and provides an early marker for gonad differentiation in zebrafish
Authors: Onichtchouk Daria , Aduroja Kristin , Belting Heinz‐Georg , Gnügge Lara , Driever Wolfgang 
Published: October 2003

AbstractAlthough mechanisms of sex differentiation have been studied intensely in mammals, insects, and worms, little is known about this process in lower vertebrates. To establish a marker for female gonad differentiation in zebrafish, we generated a transgenic line in which 412 bp from the promoter and 5′ mRNA leader of the female‐specific zebrafish zona pellucida gene zpc are fused to the coding region of green fluorescent protein (GFP). The zpc0.5:GFP transgene is expressed exclusively in oocytes, starting from the onset of female‐specific differentiation, and closely resembles the expression pattern of the wild‐type zpc. Strong GFP expression persists throughout oogenesis and is visible through the body wall of females. We have also characterized a putative upstream factor of zpc, FIGalpha, and show that distribution of FIGalpha RNA is compatible with its postulated role in the regulation of zpc. The zpc0.5:GFP transgenic line described here will be useful for studying oocyte development and the mechanisms that determine sex‐specific gene expression in the zebrafish. It is also the first promoter characterized to date to drive stable and efficient expression specifically in the zebrafish female germline. Development Dynamics, 2003. © 2003 Wiley‐Liss, Inc.
Modeling human hematopoietic and cardiovascular diseases in zebrafish
Authors: North Trista E. , Zon Leonard I. 
Published: October 2003

AbstractZebrafish have emerged as a useful vertebrate model system in which unbiased large‐scale screens have revealed hundreds of mutations affecting vertebrate development. Many zebrafish mutants closely resemble known human disorders, thus providing intriguing prospects for uncovering the genetic basis of human diseases and for the development of pharmacologic agents that inhibit or correct the progression of developmental disorders. The rapid pace of advances in genomic sequencing and map construction, in addition to morpholino targeting and transgenic techniques, have facilitated the identification and analysis of genes associated with zebrafish mutants, thus promoting the development of zebrafish as a model for human disorders. This review aims to illustrate how the zebrafish has been used to identify unknown genes, to assign function to known genes, and to delineate genetic pathways, all contributing valuable leads toward understanding human pathophysiology. Developmental Dynamics 2003. © 2003 Wiley‐Liss, Inc.
Targeted gene knockdown in zebrafish using negatively charged peptide nucleic acid mimics
Authors: Urtishak Karen A. , Choob Michael , Tian Xiaobing , Sternheim Nitzan , Talbot William S. , Wickstrom Eric , Farber Steven A. 
Published: October 2003

AbstractNegatively charged homo‐oligomers of alternating trans‐4‐hydroxy‐L‐proline/phosphonate polyamides with DNA bases (HypNA‐pPNA) display excellent hybridization properties toward DNA and RNA, while preserving the mismatch discrimination, nuclease resistance, and protease resistance of peptide nucleic acids (PNAs). Similar properties are associated with morpholino phosphorodiamidate (MO) DNA mimics, which have been used in the model vertebrate zebrafish (Danio rerio) for genome‐wide, sequence‐based, reverse genetic screens during embryonic development. We evaluated mixed sequence HypNA‐pPNAs as an alternative to MOs, and found that even a single central DNA mismatch lowered the HypNA‐pPNA melting temperature by 16°C. We then observed that the melting temperatures of HypNA‐pPNA 18‐mers hybridized to RNA 25‐mers were comparable to the melting temperatures of MO 25‐mers, and that two HypNA‐pPNA mismatches lowered the melting temperature with RNA by 18°C. In zebrafish embryos we observed that HypNA‐pPNA 18‐mers displayed comparable potency to MO 25‐mers as knockdown agents against chordin, notail, and uroD, with greater mismatch stringency. Finally we observed that a specific HypNA‐pPNA 18‐mer elicited the dharma (bozozok)‐/‐ phenotype in zebrafish embryos, which MO 25‐mers do not. HypNA‐pPNAs designed to inhibit translation of specific zebrafish RNA targets thus demonstrated stringent hybridization properties, relative to DNA and MO oligomers, and present a valuable alternative for reverse genetic studies, enabling the targeting of previously inaccessible genes. Developmental Dynamics, 2003. © 2003 Wiley‐Liss, Inc.
Imaging brain development and organogenesis in zebrafish using immobilized embryonic explants
Authors: Langenberg Tobias , Brand Michael , Cooper Mark S. 
Published: October 2003

AbstractOwing to its optical clarity and rapid rate of development, the zebrafish embryo is an ideal model system for studying the cellular mechanics of organogenesis. Unfortunately, extended time‐lapse recordings of zebrafish embryos are often disrupted by the extension and straightening of the embryonic axis, as well as movement artifacts associated with developing musculature. In addition, the embryo's massive yolk cell often prevents optical access to tissues of interest. To circumvent these imaging problems, we have developed a procedure to deflate and mechanically remove the yolk cell. A “paralyzing” agent, AMP‐PNP (a membrane‐impermeant nonhydrolyzable analog of ATP), is first injected into the embryo's contractile yolk cell. The yolk cell is then removed using sharpened tungsten needles. Deyolked embryos, or organ rudiments explanted from them, are then immobilized on a microscope coverslip using a thin plasma clot. This plasma clot immobilization allows novel mountings of the explants so that ventral, lateral, and even cross‐sectional fields of views are possible using high numerical aperture objectives. We show that isolated head rudiments undergo normal morphogenesis and gene expression for at least 1 day after being explanted into organotypic culture. These procedures can be used to study the cellular mechanics of organogenesis in “deyolked” embryos, as well as in tissues explanted from green fluorescent protein transgenic animals. Developmental Dynamics 2003. © 2003 Wiley‐Liss, Inc.
A MAGE/NDN‐like gene in zebrafish
Authors: Bischof Jocelyn M. , Ekker Marc , Wevrick Rachel 
Published: October 2003

AbstractThe human necdin/MAGE gene family has over 50 members, but most of the proteins encoded by these genes are of unknown function. We have now identified a single locus in Danio rerio that encodes a putative protein with significant coding sequence similarity to the mammalian NDN/MAGE genes. Analysis of the complete Fugu ribripes genome sequence also suggests that there is only a single MAGE‐like gene in teleost fish. mage is expressed in the larval and adult brain, specifically the retina, the medial region of the telencephalon, periventricular gray zone of the optic tectum, and most highly in the cerebellar corpus. The discovery of a zebrafish NDN/MAGE gene expressed the developing brain facilitates studies of the MAGE homology domain in vertebrate development. Developmental Dynamics, 2003. © 2003 Wiley‐Liss, Inc.
Histology‐based screen for zebrafish mutants with abnormal cell differentiation
Authors: Mohideen Manzoor‐Ali P.K. , Beckwith Lee G. , Tsao‐Wu Gladys S. , Moore Jessica L. , Wong Andrew C.C. , Chinoy Mala R. , Cheng Keith C. 
Published: October 2003

AbstractThe power of histology to define states of cell differentiation was used as the basis of a mutagenesis screen in zebrafish. In this screen, 7‐day‐old parthenogenetic half‐tetrad larvae from potential carrier females were screened for mutations affecting cell differentiation in hematoxylin and eosin‐stained tissue sections. Seven, noncomplementing, recessive mutations were found. Two mutations affect only the retina: segmented photoreceptors (spr) show a discontinuous photoreceptor cell layer; vestigial outer segments (vos) has fewer photoreceptor cells and degenerated outer segments within this cell layer. Three mutants have gut‐specific defects: the epithelial cells of kirby (kby) are replaced by ballooned cells; the intestines of stuffy (sfy) and stuffed (sfd) contain increased luminal mucus. Two mutations affect multiple organs: disordered neural retina (dnr) has disrupted retinal layering and mild nuclear abnormalities in the gut and liver; and in huli hutu (hht), the retinal cell layers are disorganized and multiple organs have mild to severe nuclear abnormalities that are reminiscent of the atypia of human neoplasia. Each mutation appears to be homozygous lethal. This screen is proof of principle for the feasibility of histologic screens to yield novel mutations, including potential models of human disease. The throughput for this type of screen may be enhanced by automation. Developmental Dynamics, 2003. © 2003 Wiley‐Liss, Inc.
Direct binding of Lef1 to sites in the boz promoter may mediate pre–midblastula‐transition activation of boz expression
Authors: Leung Tinchung , Söll Iris , Arnold Sebastian J. , Kemler Rolf , Driever Wolfgang 
Published: October 2003

AbstractThe Nieuwkoop center provides signals essential for the establishment of the dorsal gastrula organizer in vertebrates. Activation of β‐catenin is one of the events in the Nieuwkoop center that lead to activation of dorsal‐specific genes during blastula and early gastrula stages. Zebrafish bozozok (boz) mutant embryos have severe defects in axial mesoderm and anterior neuroectoderm. The boz gene is activated in the organizer in response to β‐catenin signaling, and Boz protein has been demonstrated to contribute to organizer formation by repression of ventralizing genes, including bmp2b, vega1, and vega2. Here, we investigate the timing and molecular mechanism by which boz expression is activated in the organizer. We demonstrate that boz is already expressed before midblastula transition (MBT). We further identify high‐affinity binding sites for Tcf/Lef1 within the boz promoter region. These sites, together with the finding that β‐catenin induces boz expression, indicate that transcription of boz may be activated directly by β‐catenin/Lef1. We hypothesize that pre‐MBT activation of boz may be important to build up a sufficiently strong antagonizing activity against zygotic ventralizing genes activated immediately post‐MBT. Thus, the early onset of boz expression may be crucial for organizer establishment in the presence of ubiquitous maternal activators of ventralizing genes. Developmental Dynamics, 2003. © 2003 Wiley‐Liss, Inc.
gbx2Homeobox gene is required for the maintenance of the isthmic region in the zebrafish embryonic brain
Authors: Kikuta Hiroshi , Kanai Maiko , Ito Yukiko , Yamasu Kyo 
Published: October 2003

AbstractWe isolated cDNA clones for the zebrafishgbx2gene, which is implicated in the establishment of the midbrain–hindbrain boundary (MHB) in other vertebrates. Spatially localized expression ofgbx2was observed at the MHB from 90% epiboly through to the hatching stage. Comparisons with the expression ofotx2,wnt1, andkrox20showed thatgbx2is expressed in the anterior hindbrain. Ectopic expression ofgbx2by mRNA injection caused cyclopia or truncation of the fore‐ and midbrain and severely affected isthmic and cerebellar structures, while hindbrain formation was not significantly affected. At the molecular level,gbx2suppressed the expression ofotx2in the fore/midbrain,six3in the anterior forebrain, and MHB‐specific genes such aseng2andwnt1. In contrast,gbx2did not down‐regulate the expression of the hindbrain marker genes. Therefore,gbx2specifically suppressed the formation of the entire fore/midbrain. Meanwhile, misexpression ofotx2suppressed the expression ofgbx2in the embryonic brain. Abrogation ofgbx2expression with an antisense morpholino oligonucleotide disrupted the midbrain/anterior hindbrain region, and these loss‐of‐function effects were rescued by activating the Gbx2 protein immediately after the end of gastrulation. Taken together, these results suggest that the zebrafishgbx2gene is essential for the maintenance of MHB and/or the formation of the isthmic structure during somitogenesis, rather than for the MHB establishment during gastrulation. We also suggest that other factors, includinggbx1, is required for the establishment of the MHB during gastrulation. Developmental Dynamics, 2003. © 2003 Wiley‐Liss, Inc.
Genome duplication, subfunction partitioning, and lineage divergence:Sox9in stickleback and zebrafish
Authors: Cresko William A. , Yan Yi‐Lin , Baltrus David A. , Amores Angel , Singer Amy , Rodríguez‐Marí Adriana , Postlethwait John H. 
Published: October 2003

AbstractTeleosts are the most species‐rich group of vertebrates, and a genome duplication (tetraploidization) event in ray‐fin fish appears to have preceded this remarkable explosion of biodiversity. What is the relationship of the ray‐fin genome duplication to the teleost radiation? Genome duplication may have facilitated lineage divergence by partitioning different ancestral gene subfunctions among co‐orthologs of tetrapod genes in different teleost lineages. To test this hypothesis, we investigated gene expression patterns forSox9gene duplicates in stickleback and zebrafish, teleosts whose lineages diverged early in Euteleost evolution. Most expression domains appear to have been partitioned betweenSox9aandSox9bbefore the divergence of stickleback and zebrafish lineages, but some ancestral expression domains were distributed differentially in each lineage. We conclude that some gene subfunctions, as represented by lineage‐specific expression domains, may have assorted differently in separate lineages and that these may have contributed to lineage diversification during teleost evolution. Developmental Dynamics, 2003. © 2003 Wiley‐Liss, Inc.
Neurogenic phenotype of mind bomb mutants leads to severe patterning defects in the zebrafish hindbrain
Authors: Bingham Stephanie , Chaudhari Summer , Vanderlaan Gary , Itoh Motoyuki , Chitnis Ajay , Chandrasekhar Anand 
Published: October 2003

AbstractFailure of Notch signaling in zebrafish mind bomb (mib) mutants results in a neurogenic phenotype where an overproduction of early differentiating neurons is accompanied by the loss of later‐differentiating cell types. We have characterized in detail the hindbrain phenotype of mib mutants. Hindbrain branchiomotor neurons (BMNs) are reduced in number but not missing in mib mutants. In addition, BMN clusters are frequently fused across the midline in mutants. Mosaic analysis indicates that the BMN patterning and fusion defects in the mib hindbrain arise non–cell autonomously. Ventral midline signaling is defective in the mutant hindbrain, in part due to the differentiation of some midline cells into neural cells. Interestingly, while early hindbrain patterning appears normal in mib mutants, subsequent rhombomere‐specific gene expression is completely lost. The defects in ventral midline signaling and rhombomere patterning are accompanied by an apparent loss of neuroepithelial cells in the mutant hindbrain. These observations suggest that, by regulating the differentiation of neuroepithelial cells into neurons, Notch signaling preserves a population of non‐neuronal cells that are essential for maintaining patterning mechanisms in the developing neural tube. Developmental Dynamics, 2003. © 2003 Wiley‐Liss, Inc.
Adults with learning disabilities: Differences between The Netherlands and Flanders
Authors: Ruijssenaars A.J.J.M. , Ghesquière Pol 
Published: October 2003

AbstractIn this paper, similarities and differences are outlined between adults with self reported learning disabilities (SRLD) drawn from the International Adult Literacy Survey (IALS) data on adult literacy in The Netherlands and Flanders. These results are discussed in terms of striking differences in the educational context within which the adults developed. The literacy skills of SRLD adults in The Netherlands are superior to SRLD adults in Flanders. This is interpreted in terms of societal acceptance of disability. Copyright © 2003 John Wiley & Sons, Ltd.
Adults with self‐reported learning disabilities in Slovenia: Findings from the international adult literacy survey on the incidence and correlates of learning disabilities in Slovenia
Authors: Magajna Lidija , Kavkler Marija , Ortar‐Križaj Martina 
Published: October 2003

AbstractThis study of adults with self‐reported learning disabilities (SRLD) in Slovenia is part of a larger secondary analysis of the data from the International Literacy Survey project (IALS). The purpose of the study was to examine the characteristics of 79 (2.68%) individuals who reported experiencing learning disabilities and compare them to the general population on a variety of indicators of educational background, employment status, and reading and writing activities at work and at home. The proficiency scores of the SRLD individuals were lower in all three literacy domains (prose, document and quantitative literacy). In prose literacy 77.9% of SRLD adults performed at Level 1 and only 7.8% reached the level necessary for a modern technological society. Experiencing learning disabilities was not related to gender or age, however, results showed significant differences between the levels achieved by older and younger people with SRLD. In SRLD groups aged 40 years and above, no one achieved more than the second level of literacy in any domain. Learning disabilities were reported more frequently in rural areas.SRLD groups achieve significantly lower educational attainment, and lower employment status, with a preference for manual labour or craft. These findings are of critical importance. SRLD people report that poorer literacy skills are an obstacle to their progression in employment. In the Slovene sample, the SRLD group stands out for low scores in quantitative literacy. Results show that they are less active, pick up information only auditorily or in short written form. They need more frequent help from relatives in literacy activities.Interpretation of the IALS data on SRLD presents many problems. These include amongst others, problems in terminology, different background factors, and the validity of self‐report measures. However, the study also raises many interesting challenges for future research and policy. Increasing the availability of support, assistance and counselling for adolescents and adults with learning disabilities remains a very important goal for dyslexia and LD policies in Slovenia. Copyright © 2003 John Wiley & Sons, Ltd.