bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new approach to the study of haematopoietic development in the yolk sac and embryoid bodies
Authors: Guimarães M. Jorge , Bazan J. Fernando , Zlotnik Albert , Wiles Michael V. , Grimaldi J. Christopher , Lee Frank , McClanahan Terrill 
Published: April 2021

ABSTRACT
To understand the mechanisms that control the differentiation of uncommitted mesoderm precursors into haematopoietic stem cells (HSCs) and the activation of haematopoiesis, we conducted a study to identify genes expressed at the earliest stages of both in vivo and in vitro haematopoietic development. Our strategy was to utilize Differential Display by means of the Polymerase Chain Reaction (DD-PCR) to compare patterns of gene expression between mRNA populations representing different levels of haematopoietic activity obtained from the mouse embryo, embryoid bodies (EBs) and mouse cell lines. We report the molecular cloning of two groups of genes expressed in the yolk sac: a group of genes expressed in the day-8.5 yolk sac at higher levels than in the day-8.5 embryo proper and up-regulated during EB development, and another group of day-8.5 yolk sac genes not expressed in the day-8.5 embryo proper or in EBs. Specifically, we describe the molecular cloning of the first nucleobase permease gene to be found in vertebrates, yolk sac permease-like molecule 1 (Yspl1). The Yspl1 gene has the unique property of encoding both intracellular, transmembrane and extracellular protein forms, revealing novel aspects of nucleotide metabolism that may be relevant during mammalian development.
Disruption of the mouse MRF4 gene identifies multiple waves of myogenesis in the myotome
Authors: Patapoutian Ardem , Yoon Jeong Kyo , Miner Jeffrey H. , Wang Shuling , Stark Kevin , Wold Barbara 
Published: April 2021

ABSTRACT
MRF4 (herculin/Myf-6) is one of the four member MyoD family of transcription factors identified by their ability to enforce skeletal muscle differentiation upon a wide variety of nonmuscle cell types. In this study the mouse germline MRF4 gene was disrupted by targeted recombination. Animals homozygous for the MRF4bh1 allele, a deletion of the functionally essential bHLH domain, displayed defective axial myogenesis and rib pattern formation, and they died at birth. Differences in somitogenesis between homozygous MRF4bh1 embryos and their wild-type littermates provided evidence for three distinct myogenic regulatory programs (My1-My3) in the somite, which correlate temporally and spatially with three waves of cellular recruitment to the expanding myotome. The first program (My1), marked initially by Myf-5 expression and followed by myogenin, began on schedule in the MRF4bh1/bh1 embryos at day 8 post coitum (E8). A second program (My2) was highly deficient in homozygous mutant MRF4 embryos, and normal expansion of the myotome failed. Moreover, expression of downstream muscle-specific genes, including FGF-6, which is a candidate regulator of inductive interactions, did not occur normally. The onset of MyoD expression around E10.5 in wild-type embryos marks a third myotomal program (My3), the execution of which was somewhat delayed in MRF4 mutant embryos but ultimately led to extensive myogenesis in the trunk. By E15 it appeared to have largely compensated for the defective My2 program in MRF4 mutants. Homozygous MRF4bh1 animals also showed improper rib pattern formation perhaps due to the absence of signals from cells expressing the My2 program. Finally, a later and relatively mild phenotype was detected in intercostal muscles of newborn animals.
Creating a Drosophila wing de novo, the role of engrailed, and the compartment border hypothesis
Authors: Tabata Tetsuya , Schwartz Carol , Gustavson Elizabeth , Ali Zehra , Kornberg Thomas B. 
Published: April 2021

ABSTRACT
Anterior/posterior compartment borders bisect every Drosophila imaginal disc, and the engrailed gene is essential for their function. We analyzed the role of the engrailed and invected genes in wing discs by eliminating or increasing their activity. Removing engrailed/invected from posterior wing cells created two new compartments: an anterior compartment consisting of mutant cells and a posterior compartment that grew from neighboring cells. In some cases, these compartments formed a complete new wing. Increasing engrailed activity also affected patterning. These findings demonstrate that engrailed both directs the posterior compartment pathway and creates the compartment border. These findings also establish the compartment border as the pre-eminent organizational feature of disc growth and patterning.
Establishment of left-right asymmetry in the Caenorhabditis elegans embryo: a multistep process involving a series of inductive events
Authors: Hutter Harald , Schnabel Ralf 
Published: April 2021

ABSTRACT
Bilateral pairs of blastomeres derived from the founder cell AB, the anterior blastomere of the 2-cell stage, in the Caenorhabditis elegans embryo are initially equivalent in their developmental potential. Recently, we showed that an induction at the 12-cell stage by a blastomere called MS is necessary to establish the differences between left and right pairs of blastomeres in the anterior part of the embryo. Further analysis of the process of creating left-right asymmetry reveals that the induction at the 12-cell stage is only the first of a series of inductions establishing the left- right asymmetry of the embryo. We describe here two further inductions that create additional asymmetries in the posterior part of the embryo. One induction occurs at the 24-cell stage among AB descendants themselves. This induction is restricted to the left side of the embryo as a consequence of the fate changes induced by MS at the 12- cell stage. The second induction requires again blastomeres of the MS lineage and also occurs around the 24-cell stage. Together these inductions establish the fate differences observed in the development of left-right pairs of blastomeres in the embryo.
Effect of polysialic acid on the behavior of retinal ganglion cell axons during growth into the optic tract and tectum
Authors: Yin Xinghua , Watanabe Michiko , Rutishauser Urs 
Published: April 2021

ABSTRACT
We have demonstrated previously that the polysialic acid (PSA) moiety of the neural cell adhesion molecule (NCAM) can regulate peripheral nerve branching during development. In particular, it was found that specific enzymatic removal of PSA from motor axons causes them to form tight fascicles that are less responsive to normal guidance cues. In the present study, the role of PSA in the behavior of axons in the central nervous system has been examined through an analysis of chick optic axons during development. Unlike peripheral axons, which generally grow in a PSA-free environment, PSA was found to be present both on retinal ganglion cell axons and their environment in the tract and tectum. Furthermore, the enzymatic removal of PSA from the optic axons caused them to defasciculate in the tract/tectal region. This response was morphologically similar to targeting corrections made by these axons at a later stage when PSA levels have decreased, suggesting that the PSA may serve to shield them from responding prematurely to some guidance cues in their target region.
A Drosophila insulator protein facilitates dosage compensation of the X chromosome mini-white gene located at autosomal insertion sites
Authors: Roseman Robin R. , Swan Jeffrey M. , Geyer Pamela K. 
Published: April 2021

ABSTRACT
The suppressor of Hairy-wing [su(Hw)] gene encodes a zinc finger protein that binds to a repeated motif in the gypsy retrotransposon. These DNA sequences, called the su(Hw)binding region, have properties of an insulator region because they (1) disrupt enhancer/silencer function in a position-dependent manner and (2) protect the mini-white gene from both euchromatic and heterochromatic position effects. To gain further insights into the types of position effects that can be insulated, we determined the effects of the su(Hw)-binding region on dosage compensation of the X-linked mini-white gene. Dosage compensation is the process that equalizes the unequal content of X-linked genes in males and females by increasing the X-linked transcription level twofold in males. Transposition of X-linked genes to the autosomes commonly results in incomplete dosage compensation, indicating that the distinct male X chromatin environment is important for this process. We found that dosage compensation of autosomally integrated mini-white genes flanked by su(Hw)-binding regions was greatly improved, such that complete or nearly complete compensation was observed at the majority of insertion sites. The su(Hw) protein was essential for this enhanced dosage compensation because in a su(Hw) mutant background compensation was incomplete. These experiments provide evidence that the su(Hw)-binding region facilitates dosage compensation of the mini-white gene on the autosomes. This may result from protection of the miniwhite gene from a negative autosomal chromatin environment.
Neurofibromin-deficient fibroblasts fail to form perineurium in vitro
Authors: Rosenbaum Thorsten , Boissy Ying L. , Kombrinck Keith , Brannan Camilynn I. , Jenkins Nancy A. , Copeland Neal G. , Ratner Nancy 
Published: April 2021

ABSTRACT
To identify cell type(s) that might contribute to nerve sheath tumors (neurofibromas) in patients with neurofibromatosis type 1, we generated cell cultures containing neurons, Schwann cells and fibroblasts from transgenic mouse embryos in which the type 1 neurofibromatosis gene was disrupted by homologous recombination (Brannan et al. (1994)Genes Development, 8,1019-1029). Normal fascicle formation by perineurial cells failed to occur in the absence of neurofibromin. Fascicles were reduced in number and showed abnormal morphology when normal neurons and Schwann cells were cultured up to 37 days with fibroblasts lacking neurofibromin. Proliferation was increased in a majority of fibroblast cell strains analyzed from embryos lacking neurofibromin. These observations suggest that mutations in the neurofibromatosis type 1 gene affect fibroblast behavior that might contribute to neurofibroma formation in patients with neurofibromatosis type 1.
Vertebrate retinal ganglion cells are selected from competent progenitors by the action of Notch
Authors: Austin Christopher P. , Feldman Douglas E. , Ida James A. , Cepko Constance L. 
Published: April 2021

ABSTRACT
The first cells generated during development of the vertebrate retina are the ganglion cells, the projection neurons of the retina. Although they are one of the most intensively studied cell types within the central nervous system, little is known of the mechanisms that determine ganglion cell fate. We demonstrate that ganglion cells are selected from a large group of competent progenitors that comprise the majority of the early embryonic retina and that differentiation within this group is regulated by Notch. Notch activity in vivo was diminished using antisense oligonucleotides or augmented using a retrovirally transduced constitutively active allele of Notch. The number of ganglion cells produced was inversely related to the level of Notch activity. In addition, the Notch ligand Delta inhibited retinal progenitors from differentiating as ganglion cells to the same degree as did activated Notch in an in vitro assay. These results suggest a conserved strategy for neurogenesis in the retina and describe a versatile in vitro and in vivo system with which to examine the action of the Notch pathway in a specific cell fate decision in a vertebrate.
Nodal-related signals induce axial mesoderm and dorsalize mesoderm during gastrulation
Authors: Jones C. Michael , Kuehn Michael R. , Hogan Brigid L. M. , Smith James C. , Wright Christopher V. E. 
Published: April 2021

ABSTRACT
Mouse embryos homozygous for a null mutation in nodal arrest development at early gastrulation and contain little or no embryonic mesoderm. Here, two Xenopus nodalrelated genes (Xnr-1 and Xnr-2) are identified and shown to be expressed transiently during embryogenesis, first within the vegetal region of late blastulae and later in the marginal zone during gastrulation, with enrichment in the dorsal lip. Xnrs and mouse nodal function as dosedependent dorsoanterior and ventral mesoderm inducers in whole embryos and explanted animal caps. Using a plasmid vector to produce Xnr proteins during gastrulation, we show that, in contrast to activin and other TGFβ-like molecules, Xnr-1 and Xnr-2 can dorsalize ventral marginal zone explants and induce muscle differentiation. Xnr signalling also rescues a complete embryonic axis in UV-ventralized embryos. The patterns of Xnr expression, the activities of the proteins and the phenotype of mouse nodal mutants, all argue strongly that a signaling pathway involving nodal, or nodal-related peptides, is an essential conserved element in mesoderm differentiation associated with vertebrate gastrulation and axial patterning.
Segmental migration of trunk neural crest: time-lapse analysis reveals a role for PNA-binding molecules
Authors: Krull Catherine E. , Collazo Andres , Fraser Scott E. , Bronner-Fraser Marianne 
Published: April 2021

ABSTRACT
Trunk neural crest cells migrate through the somites in a striking segmental fashion, entering the rostral but not caudal sclerotome, via cues intrinsic to the somites. Attempts to define the molecular bases of these cues have been hampered by the lack of an accessible assay system. To examine trunk neural crest migration over time and to perturb candidate guiding molecules, we have developed a novel explant preparation. Here, we demonstrate that trunk regions of the chicken embryo, placed in explant culture, continue to develop apparently normally for 2 days. Neural crest cells, recognized by prelabeling with DiI or by poststaining with the HNK-1 antibody, migrate in the somites of the explants in their typical segmental pattern. Furthermore, this paradigm allows us to follow trunk neural crest migration in situ for the first time using lowlight-level videomicroscopy. The trajectories of individual neural crest cells were often complex, with cells migrating in an episodic mode encompassing forward, backward and lateral movements. Frequently, neural crest cells migrated in close-knit groups of 2–4 cells, moving at mean rates of migration of 10–14 μm/hour. Treatment of the explants with the lectin peanut agglutinin (PNA) both slowed the rate and altered the pattern of neural crest migration. Neural crest cells entered both the rostral and caudal halves of the sclerotome with mean rates of migration ranging from 6 to 13 μm/hour. These results suggest that peanut agglutinin-binding molecules are required for the segmental patterning of trunk neural crest migration. Because this approach permits neural crest migration to be both observed and perturbed, it offers the promise of more direct assays of the factors that influence neural crest development.
Role of Notch and achaete-scute complex in the expression of Enhancer of split bHLH proteins
Authors: Jennings Barbara , Celis Jesus de , Delidakis Christos , Preiss Anette , Bray Sarah 
Published: April 2021

ABSTRACT
The proteins encoded by Notch and the Enhancer of split complex are components of a cell-cell interaction mechanism which is important in many cell fate decisions throughout development. One such decision is the formation of the sensory organ precursor cell during the development of the peripheral nervous system in Drosophila. Cells acquire the potential to be neural through the expression of the proneural genes, and the Notch pathway is required to limit neural fate to a single cell from a proneural cluster. However, despite extensive analysis, the precise pathways linking the proneural with Notch and Enhancer of split gene functions remain obscure. For example, it has been suggested that achaete-scute complex proteins directly activate Enhancer of split genes leaving the action of Notch in the pathway unclear. Using monoclonal antibodies that recognise products of the Enhancer of split complex, we show that these proteins accumulate in the cells surrounding the developing sensory organ precursor cell and that their expression is dependent on the activity of Notch and does not directly correlate with expression of Achaete. We further clarify the pathway by showing that ubiquitous expression of an activated Notch receptor leads to widespread accumulation of Enhancer of split proteins even in the absence of achaete-scute complex proteins. Thus Enhancer of split protein expression in response to Notch activity does not require achaete-scute complex proteins.
wingless is required for the formation of a subset of muscle founder cells during Drosophila embryogenesis
Authors: Baylies M. K. , Arias A. Martinez , Bate M. 
Published: April 2021

ABSTRACT
The final pattern of the Drosophila larval body wall muscles depends critically on the prior segregation of muscle founder cells. We would like to understand the underlying molecular mechanisms which ensure the precise allocation and placement of these muscle founder cells. We have begun our analysis by examining the role of the segment polarity genes, known to be involved in the patterning of the ectoderm. Mutations in only one member of this class, wingless (wg), lead to the complete loss of a subset of muscle founder cells characterised by the expression of S59. Using the GAL4-targetted expression system, we find that Wingless, a secreted glycoprotein and well characterized signalling molecule, acts directly on the mesoderm to ensure the formation of S59-expressing founder cells. Moreover, we present evidence that Wg can signal across germ layers and that, in the wild-type embryo, Wg from the ectoderm could constitute an inductive signal for the initiation of the development of a subset of somatic muscles.
The porcupine gene is required for wingless autoregulation in Drosophila
Authors: Manoukian Armen S. , Yoffe Kenneth B. , Wilder Elizabeth L. , Perrimon Norbert 
Published: April 2021

ABSTRACT
The Drosophila segment polarity gene wingless (wg) is required in the regulation of engrailed (en) expression and the determination of cell fates in neighboring cells. This paracrine wg activity also regulates transcription of wg itself, through a positive feedback loop including en activity. In addition, wg has a second, more direct autoregulatory requirement that is distinct from the en-dependent feedback loop. Four gene products, encoded by armadillo (arm), dishevelled (dsh), porcupine (porc) and zeste-white 3 (zw3), have been previously implicated as components of wg paracrine signaling. Here we have used three different assays to assess the requirements of these genes in the more direct wg autoregulatory pathway. While the activities of dsh, zw3 and arm appear to be specific to the paracrine feedback pathway, the more direct autoregulatory pathway requires porc.
Differential effects of combined trk receptor mutations on dorsal root ganglion and inner ear sensory neurons
Authors: Minichiello Liliana , Piehl Fredrik , Vazquez Esther , Schimmang Thomas , Hökfelt Tomas , Represa Juan , Klein Rüdiger 
Published: April 2021

ABSTRACT
We have generated double mutant mice deficient in pairs of two different Trk receptors and have analysed the effects on survival and differentiation of dorsal root ganglion (DRG), inner ear cochlear and vestibular sensory neurons. In most combinations of mutant trk alleles, the defects observed in double compared to single mutant mice were additive. However, double homozygous trkA−/−;trkB−/− DRG and trkB−/−;trkC−/− vestibular neurons showed the same degree of survival as single trkA−/− and trkB−/− mice, respectively, suggesting that those neurons required both Trk signaling pathways for survival. In situ hybridisation analysis of DRG neurons of double mutant mice revealed differential expression of excitatory neuropeptides. Whereas calcitonin-gene-related peptide expression correlated with the trkA phenotype, substance P expression was detected in all combinations of double mutant mice. In the inner ear, TrkB- and TrkC-dependent neurons were shown to at least partially depend on each other for survival, most likely indirectly due to abnormal development of their common targets. This effect was not observed in DRGs, where neurons depending on different Trk receptors generally innervate different targets.
Role of the morphogenetic furrow in establishing polarity in the Drosophila eye
Authors: Chanut Françoise , Heberlein Ulrike 
Published: April 2021

ABSTRACT
The Drosophila retina is a crystalline array of 800 ommatidia whose organization and assembly suggest polarization of the retinal epithelium along anteroposterior and dorsoventral axes. The retina develops by a stepwise process following the posterior-to-anterior progression of the morphogenetic furrow across the eye disc. Ectopic expression of hedgehog or local removal of patched function generates ectopic furrows that can progress in any direction across the disc leaving in their wake differentiating fields of ectopic ommatidia. We have studied the effect of these ectopic furrows on the polarity of ommatidial assembly and rotation. We find that the anteroposterior asymmetry of ommatidial assembly parallels the progression of ectopic furrows, regardless of their direction. In addition, ommatidia developing behind ectopic furrows rotate coordinately, forming equators in various regions of the disc. Interestingly, the expression of a marker normally restricted to the equator is induced in ectopic ommatidial fields. Ectopic equators are stable as they persist to adulthood, where they can coexist with the normal equator. Our results suggest that ectopic furrows can impart polarity to the disc epithelium, regarding the direction of both assembly and rotation of ommatidia. We propose that these processes are polarized as a consequence of furrow propagation, while more global determinants of dorsoventral and anteroposterior polarity may act less directly by determining the site of furrow initiation.
Anterior-posterior subdivision and the diversification of the mesoderm in Drosophila
Authors: Borkowski Olga M. Dunin , Brown Nicholas H. , Bate Michael 
Published: April 2021

ABSTRACT
We have used a novel cell marker, in which the twist promoter directs the synthesis of the cell surface protein CD2 (twi-CD2) to examine the development of the mesoderm in the Drosophila embryo after gastrulation and to locate the progenitor cell populations for different meso- dermal derivatives. We find that the early mesoderm in each segment is divided into a more anterior region with relatively low levels of twist and twi-CD2 expression and a more posterior region where twist and twi-CD2 expression are high. This subdivision coincides with regional assignments of cells to form different progenitors: dorsal anterior cells invaginate to form an internal layer from which the visceral mesoderm is derived. Ventral anterior cells form progenitors of mesodermal glial cells. Dorsal posterior cells form heart. Ventral and dorsal posterior cells form somatic muscles. We conclude that the metamerically repeated anterior-posterior subdivision of the mesoderm is an essential element in laying out the pattern of mesodermal progenitor cells and in distinguishing between an internal cell layer which will give rise to the progenitors of visceral muscles and an external layer which will generate the somatic muscles and the heart.