bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell autonomous functions of the receptor tyrosine kinase TIE in a late phase of angiogenic capillary growth and endothelial cell survival during murine development
Authors: Partanen Juha , Puri Mira C. , Schwartz Lois , Fischer Klaus-Dieter , Bernstein Alan , Rossant Janet 
Published: April 2021

ABSTRACT
TIE is a receptor tyrosine kinase expressed in both mature endothelial cells and their precursors, as well as in some hematopoietic cells. Mouse embryos homozygous for a disrupted Tie allele die at midgestation due to impaired endothelial cell integrity and resulting hemorrhage. Here we have performed chimeric analysis to study further the function of the murine TIE in the development of embryonic vasculature and in the hematopoietic system. Cells lacking a functional Tie gene (tielcztielczn– cells) contributed to the embryonic vasculature at E10.5 as efficiently as cells heterozygous for a targeted Tie allele (tielcz+ cells). Thus, TIE does not play a significant role in vasculogenesis or in early angiogenic processes, such as formation of the intersomitic arteries and limb bud vascularization. At E15.5 tielcztielczn– cells still readily contributed to major blood vessels and to endothelial cells of organs such as lung and heart, which have been suggested to be vascularized by angioblast differentiation. In contrast, the tielcztielczn– cells were selected against in the capillary plexuses of several angiogenically vascularized tissues, such as brain and kidney. Our results thus support,a role for TIE in late phases of angiogenesis but not vasculogenesis. Furthermore, the results suggest that different mechanisms regulate early and late angiogenesis and provide support for a model of differential organ vascularization by vasculogenic or angiogenic processes. Analysis of adult chimeras suggested that TIE is required to support the survival or proliferation of certain types of endothelial cells demonstrating heterogeneity in the growth/survival factor requirements in various endothelial cell populations.
Chimeric analysis of adult hematopoietic cell populations, including peripheral platelets and bone marrow progenitor cells, revealed that tielcztielczn– cells were able to contribute to these cell types in a way indistinguishable from tielcz+ or wild-type cells. Thus, the primary function of TIE appears to be restricted to the endothelial cell lineage.
The Xvent-2 homeobox gene is part of the BMP-4 signalling pathway controling dorsoventral patterning of Xenopus mesoderm
Authors: Onichtchouk Darya , Gawantka Volker , Dosch Roland , Delius Hajo , Hirschfeld Kirsten , Blumenstock Claudia , Niehrs Christof 
Published: April 2021

ABSTRACT
We describe a novel Xenopus homeobox gene, Xvent-2, which together with the previously identified homeobox gene Xvent-1, defines a novel class of homeobox genes. vent genes are related by sequence homology, expression pattern and gain-of-function phenotype. Evidence is presented for a role of Xvent-2 in the BMP-4 pathway involved in dorsoventral patterning of mesoderm. (1) Xvent-2 is expressed in regions that also express BMP-4. (2) Xvent-2 and BMP-4 interact in a positive feedback loop. (3) Xvent-2 ventralizes dorsal mesoderm in a dose-dependent manner resulting in phenoytpes ranging from microcephaly to Bauchstück pieces, as does BMP-4. (4) Like BMP-4 and gsc, Xvent-2 and gsc are able to interact in a crossregulatory loop to suppress each other. (5) Microinjection of Xvent-2 mRNA can rescue dorsalization by a dominant-negative BMP-4 receptor. The results suggest that Xvent-2 functions in the BMP-4 signalling pathway that antagonizes the Spemann organizer.
Early gene expression along the animal-vegetal axis in sea urchin embryoids and grafted embryos
Authors: Ghiglione Christian , Emily-Fenouil Francoise , Chang Patrick , Gache Christian 
Published: April 2021

ABSTRACT
The HE gene is the earliest strictly zygotic gene activated during sea urchin embryogenesis. It is transiently expressed in a radially symmetrical domain covering the animal-most two-thirds of the blastula. The border of this domain, which is orthogonal to the primordial animal-vegetal axis, is shifted towards the animal pole in Li+-treated embryos. Exogenous micromeres implanted at the animal pole of whole embryos, animal or vegetal halves do not modify the extent and localization of the HE expression domain. In grafted embryos or animal halves, the Li+ effect is not affected by the presence of ectopic micromeres at the animal pole. A Li+-induced shift of the border, similar to that seen in whole embryos, occurs in embryoids develop-ing from animal halves isolated from 8-cell stage embryos or dissected from unfertilised eggs. Therefore, the spatial restriction of the HE gene is not controlled by the inductive cascade emanating from the micromeres and the pattern-ing along the AV-axis revealed by Li+ does not require interactions between cells from the animal and vegetal halves. This suggests that maternal primary patterning in the sea urchin embryo is not limited to a small vegetal center but extends along the entire AV axis.
PAR-2 is asymmetrically distributed and promotes association of P granules and PAR-1 with the cortex in C. elegans embryos
Authors: Boyd Lynn , Guo Su , Levitan Diane , Stinchcomb Dan T. , Kemphues Kenneth J. 
Published: April 2021

ABSTRACT
The par genes participate in the process of establishing cellular asymmetries during the first cell cycle of Caenorhabditis elegans development. The par-2 gene is required for the unequal first cleavage and for asymmetries in cell cycle length and spindle orientation in the two resulting daughter cells. We have found that the PAR-2 protein is present in adult gonads and early embryos. In gonads, the protein is uniformly distributed at the cell cortex, and this subcellular localization depends on micro-filaments. In the one-cell embryo, PAR-2 is localized to the posterior cortex and is partitioned into the posterior daughter, P1, at the first cleavage. PAR-2 exhibits a similar asymmetric cortical localization in P1, P2, and P3, the asym-metrically dividing blastomeres of germ line lineage. This distribution in embryos is very similar to that of PAR-1 protein.
By analyzing the distribution of the PAR-2 protein in various par mutant backgrounds we found that proper asymmetric distribution of PAR-2 depends upon par-3 activity but not upon par-1 or par-4. par-2 activity is required for proper cortical localization of PAR-1 and this effect requires wild-type par-3 gene activity. We also find that, although par-2 activity is not required for posterior localization of P granules at the one-cell stage, it is required for proper cortical association of P granules in P1.
Appropriate pattern formation following regulative regeneration in the hindbrain neural tube
Authors: Díaz Carmen , Glover Joel C. 
Published: April 2021

ABSTRACT
Patterns of neuronal differentiation and axon outgrowth were examined in regenerated neural tissue of the hindbrain of the chicken embryo. Specific regions of the hindbrain neural tube corresponding to identified rhom-bomeres were selectively removed unilaterally by micro-surgery. Of the embryos that survived, about 35% exhibited regulative regeneration, wherein the missing hemi-rhombomere was reconstituted to normal size and morphology through compensatory proliferation and migration from adjacent tissue. The capacity for regener-ation depended on the embryonic stage at which the ablation was performed and on whether the midline floor plate was included in the ablation. Ablations performed prior to the formation of morphologically overt rhom-bomere boundaries led to significantly lower frequencies of regulative regeneration than ablations performed after the formation of boundaries. Ablations that included the floor plate led to significantly lower frequencies of regulative regeneration than ablations sparing the floor plate. Regu-lative regeneration was also observed at low frequency following excision of an entire rhombomere.
Within the regenerated hemi-rhombomere, identified neuron groups appeared in their normal positions and dif-ferentiated normal patterns of migration and axon outgrowth. The fidelity of this patterning, however, depended on the mediolateral position of the neuron group, being more reliable for neuron groups in the basal plate than in the alar plate. These results confirm the extensive regulative potential of the neural tube and demonstrate the capacity for appropriately patterned cellular differen-tiation within the regenerated tissue.
Keratinocyte growth factor and its receptor are involved in regulating early lung branching
Authors: Post Martin , Souza Patricia , Liu Jason , Tseu Irene , Wang Jinxia , Kuliszewski Maciej , Tanswell A. Keith 
Published: April 2021

ABSTRACT
Lung branching morphogenesis depends on mesenchymalepithelial tissue interactions. Keratinocyte growth factor (KGF) has been implicated to be a regulator of these tissue interactions. In the present study, we investigated the role of KGF in early rat lung organogenesis. Reverse transcriptase-polymerase chain reaction analysis revealed KGF mRNA expression in the mesenchymal component of the 13-day embryonic lung, while message for KGF receptor (KGFR) was expressed in the epithelium, confirming the paracrine nature of KGF/KGFR axis. Antisense KGF oligonucleotides inhibited DNA synthesis of embryonic lung explants. This inhibitory effect of antisense KGF was partially reversed by the addition of exogenous KGF. Recombinant KGF was mitogenic for 13-day isolated embryonic lung epithelial cells. Medium conditioned by 13-day lung mesenchymal cells also stimulated DNA synthesis of 13-day embryonic lung epithelial cells. This stimulatory effect was partially abrogated by a neutralizing KGF antibody. The number of terminal buds of lung explants cultured in the presence of antisense KGF oligonucleotides was significantly reduced compared to control explants. Exogenous KGF partially abrogated the inhibitory effect of antisense KGF on early lung branching. Sense or scrambled KGF oligonucleotides had no inhibitory effect on lung growth and branching. Addition of neutralizing KGF antibodies to the explants also reduced the degree of branching, while non-immune IgG and neutralizing acidic FGF antibodies had no effect. Explants incubated with antisense oligonucleotides targeted to the initiation site of translation of both the splice variants of the fibroblast growth factor receptor-2 (FGFR2) gene, KGFR and bek, exhibited a similar reduction in lung branching as observed with antisense KGF oligonucleotides. Antisense KGFR-specific oligonucleotides dramatically inhibited lung branching, while exposure of explants to antisense bek-specific oligonucleotides resulted in reduced branching albeit to a lesser degree than that observed with antisense KGFR-specific oligonucleotides. Neither sense nor scrambled KGFR-specific oligonucleotides had any effect on early lung branching. These results suggest that the KGF/KGFR system has a critical role in early lung organogenesis.
Neuronal cell migration in C. elegans: regulation of Hox gene expression and cell position
Authors: Harris Jeanne , Honigberg Lee , Robinson Naomi , Kenyon Cynthia 
Published: April 2021

ABSTRACT
In C. elegans, the Hox gene mab-5, which specifies the fates of cells in the posterior body region, has been shown to direct the migrations of certain cells within its domain of function. mab-5 expression switches on in the neuroblast QL as it migrates into the posterior body region. mab-5 activity is then required for the descendants of QL to migrate to posterior rather than anterior positions. What information activates Hox gene expression during this cell migration? How are these cells subsequently guided to their final positions? We address these questions by describing four genes, egl-20, mig-14, mig-1 and lin-17, that are required to activate expression of mab-5 during migration of the QL neuroblast. We find that two of these genes, egl-20 and mig-14, also act in a mab-5-independent way to determine the final stopping points of the migrating Q descendants. The Q descendants do not migrate toward any obvious physical targets in wild-type or mutant animals. Therefore, these genes appear to be part of a system that positions the migrating Q descendants along the anteroposterior axis.
A conserved region of engrailed, shared among all en-, gsc-, Nk1-, Nk2- and msh-class homeoproteins, mediates active transcriptional repression in vivo
Authors: Smith Sheryl T. , Jaynes James B. 
Published: April 2021

ABSTRACT
The engrailed homeoprotein is a dominantly acting or ‘active’ transcriptional repressor both in cultured cells and in vivo. When retargeted via a homeodomain swap to the endogenous fushi tarazu gene (ftz), it actively represses it, resulting in a ftz mutant phenocopy. We have mapped functional regions of engrailed using this in vivo repression assay. In addition to a region containing an active repression domain identified in cell culture assays (K. Han and J. L. Manley, 1993), we find that two evolutionarily conserved regions contribute to activity. The one of these that does not flank the HD is particularly crucial to repression activity in vivo. We find that this domain is present not only in all engrailed-class homeo-proteins but also in all known members of several other classes, including goosecoid, Nk1, Nk2 and msh. Thus engrailed’s active repression function in vivo is dependent on a highly conserved interaction that was established early in the evolution of the homeobox gene superfamily. We further show using rescue transgenes that the widely conserved in vivo repression domain is required for the normal function of engrailed in the embryo.
Undifferentiated cells in the developing Drosophila eye influence facet assembly and require the Fat facets ubiquitin-specific protease
Authors: Huang Yongzhao , Fischer-Vize Janice A. 
Published: April 2021

ABSTRACT
The Drosophila compound eye develops by a complex series of cell interactions where multiple positive and inhibitory cues guide cells in each facet into their positions and fates. The results of many genetic and molecular experiments have led to the view that facet assembly is directed by cells within developing ommatidial preclusters. Here fat facets mutants and the cloned fat facets gene were used to show that, in order to limit the number of photoreceptors in a facet to eight, undifferentiated cells surrounding assembling facets send an inhibitory signal to extraneous cells within the facet preclusters. Generation of the inhibitory signal requires the ubiquitin-specific protease encoded by the fat facets gene and is thus regulated by ubiquitin-dependent proteolysis.
Targeted disruption of the Wnt2 gene results in placentation defects
Authors: Monkley Susan J. , Delaney Stephen J. , Pennisi David J. , Christiansen Jeffrey H. , Wainwright Brandon J. 
Published: April 2021

ABSTRACT
Wnt genes have been implicated in a range of developmental processes in the mouse including the patterning of the central nervous system and limbs. Reported here for the first time is the expression of Wnt2 in the early heart field of 7.5–8.5 dpc (days post-coitum) mouse embryos, making Wnt2 a potentially useful gene marker for the early stages of heart development. Expression was also detected in the allantois from 8.0 dpc and at later stages in the placenta and umbilicus. Mice deficient in Wnt2, generated by gene targeting, displayed runting and approximately 50% died perinatally. Histological analysis revealed alterations in the size and structure of placentas from these mice from 14.5 dpc. The placental defects were associated primarily with the labyrinthine zone and included oedema and tissue disruption and accumulation of maternal blood in large pools. There was also an apparent decrease in the number of foetal capillaries and an increase in the amount of fibrinoid material in the Wnt2 mutant placentas. These results suggest that Wnt2 is required for the proper vascularisation of the mouse placenta and the placental defects in Wnt2-deficient mice result in a reduction in birthweight and perinatal lethality.
Pax2 contributes to inner ear patterning and optic nerve trajectory
Authors: Torres Miguel , Gómez-Pardo Emilia , Gruss Peter 
Published: April 2021

ABSTRACT
During gestation, the paired box-containing gene Pax2 is expressed in the mid-hindbrain area, developing eye and inner ear. We generated Pax2 null mutant mice, which show the requirement of Pax2 for the establishment of axonal pathways along the optic stalks and ventral diencephalon. In mutant brains, the optic tracts remain totally ipsilateral due to agenesis of the optic chiasma. Furthermore, Pax2 mutants show extension of the pigmented retina into the optic stalks and failure of the optic fissure to close resulting in coloboma. In the inner ear, Pax2 mutants show agenesis of the cochlea and the spiral ganglion, i.e., the parts of the organ responsible for auditory function and in whose primordium Pax2 is expressed. Our results identify Pax2 as a major regulator of patterning during organogenesis of the eye and inner ear and indicate its function in morphogenetic events required for closure of the optic fissure and neural tube.
The regeneration of the cephalic neural crest, a problem revisited: the regenerating cells originate from the contralateral or from the anterior and posterior neural fold
Authors: Couly Gérard , Grapin-Botton Anne , Coltey Pierre , Douarin Nicole M. Le 
Published: April 2021

ABSTRACT
The mesencephalic and rhombencephalic levels of origin of the hypobranchial skeleton (lower jaw and hyoid bone) within the neural fold have been determined at the 5-somite stage with a resolution corresponding to each single rhombomere, by means of the quail-chick chimera technique. Expression of certain Hox genes (Hoxa-2, Hoxa-3 and Hoxb-4) was recorded in the branchial arches of chick and quail embryos at embryonic days 3 (E3) and E4. This was a pre-requisite for studying the regeneration capacities of the neural crest, after the dorsal neural tube was resected at the mesencephalic and rhombencephalic level. We found first that excisions at the 5-somite stage extending from the mid-mesencephalon down to r8 are followed by the regeneration of neural crest cells able to compensate for the deficiencies so produced. This confirmed the results of previous authors who made similar excisions at comparable (or older) developmental stages. When a bilateral excision was followed by the unilateral homotopic graft of the dorsal neural tube from a quail embryo, thus mimicking the situation created by a unilateral excision, we found that the migration of the grafted unilateral neural crest (quail-labelled) is bilateral and compensates massively for the missing crest derivatives. The capacity of the intermediate and ventral neural tube to yield neural crest cells was tested by removing the chick rhombencephalic neural tube and replacing it either uni- or bilaterally with a ventral tube coming from a stage-matched quail. No neural crest cells exited from the ventral neural tube but no deficiency in neural crest derivatives was recorded. Crest cells were found to regenerate from the ends of the operated region. This was demonstrated by grafting fragments of quail neural fold at the extremities of the excised territory. Quail neural crest cells were seen migrating longitudinally from both the rostral and caudal ends of the operated region and filling the branchial arches located inbetween. Comparison of the behaviour of neural crest cells in this experimental situation with that showed by their normal fate map revealed that crest cells increase their proliferation rate and change their migratory behaviour without modifying their Hox code.
Structure of the insect head as revealed by the EN protein pattern in developing embryos
Authors: Rogers Bryan T. , Kaufman Thomas C. 
Published: April 2021

ABSTRACT
The structure of the insect head has long been a topic of enjoyable yet endless debate among entomologists. More recently geneticists and molecular biologists trying to better understand the structure of the head of the Dipteran Drosophila melanogaster have joined the discourse extrapolating from what they have learned about Drosophila to insects in general. Here we present the results of an investigation into the structure of the insect head as revealed by the distribution of engrailed related protein (Engrailed) in the insect orders Diptera, Siphonaptera, Orthoptera and Hemiptera. The results of this comparative embryology in conjunction with genetic experiments on Drosophila melanogaster lead us to conclude: (1) The insect head is composed of six Engrailed accumulating segments, four postoral and two preoral. The potential seventh and eighth segments (clypeus or labrum) do not accumulate Engrailed. (2) The structure known as the dorsal ridge is not specific to the Diptera but is homologous to structures found in other insect orders. (3) A part of this structure is a single segment-like entity composed of labial and maxillary segment derivatives which produce the most anterior cuticle capable of taking a dorsal fate. The segments anterior to the maxillary segment produce only ventral structures. (4) As in Drosophila, the process of segmentation of the insect head is fundamentally different from the process of segmentation in the trunk. (5) The pattern of Engrailed accumulation and its presumed role in the specification and development of head segments appears to be highly conserved while its role in other pattern formation events and tissue-specific expression is variable. An overview of the pattern of Engrailed accumulation in developing insect embryos provides a basis for discussion of the generality of the parasegment and the evolution of Engrailed patterns.
A relationship between apoptosis and flow during programmed capillary regression is revealed by vital analysis
Authors: Meeson Annette , Palmer Michelle , Calfon Marcella , Lang Richard 
Published: April 2021

ABSTRACT
Previous analyses of developmentally programmed capillary regression suggested two distinct causes of vascular endothelial cell (VEC) death. The first appeared to be macrophage-dependent (Lang, R. A. and Bishop, M.
J. (1993) Cell 74, 453-462) while the second was proposed to result from cessation of blood flow (Lang, R. A., Lustig, M., Francois, F., Sellinger, M. and Plesken, H. (1994). Development 120, 3395-3403). Combined, these analyses suggested a model in which initial, macrophage-mediated endothelial cell apoptosis blocked blood flow within a capillary segment and, as a consequence, caused apoptosis of all remaining cells in the affected segment.
In the current study, we have tested this model using a new method that combines vital and histological analyses as a means of determining the fate of whole capillary segments and individual cells in vivo. This technique revealed that one of the first events in regression was the apoptosis of a single VEC in otherwise normal, flowing capillary segments (initiating apoptosis). These isolated, dying VECs projected into and restricted the capillary lumen, imposing either a temporary or permanent block to blood flow. Following cessation of flow, synchronous apoptosis of VECs occurred (secondary apoptosis). In addition, a quantitative analysis revealed a reciprocal relationship between plasma flow and VEC apoptosis. These observations are consistent with a model for capillary regression in which macrophages induce apoptosis in a limited number of VECs and, as a consequence of a block to blood flow, also cause apoptosis in those remaining.