bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role in neural patterning of translation initiation factor eIF4AII; induction of neural fold genes
Authors: Morgan Richard , Sargent Michael G. 
Published: April 2021

ABSTRACT
Expression of the RNA-helicase translation initiation factor, eIF4AII, in animal cap explants of Xenopus specifically upregulates genes expressed early in the neural plate border such as Xsna, Xslu, Pax-3 and XANF and also the cement gland marker XCG-1. eIF4AII is expressed specifically in the prospective neurectoderm from stage 11.5 and appears to have a significant role in mediating early patterning of the neurectoderm. It is induced by all known neural inducing regimes including secreted factors such as noggin, follistatin and chordin, transcription factors such as XlPou-2 and constructs that overcome repression of neural induction (tBMP-4R, lim-m3 and Xbra Δ 304). It is also upregulated when neurulization occurs in embryonic ectoderm that has been disaggregated and reaggregated. While high amounts of injected mRNA of the neural inducers noggin, tBMP-4R and Xlpou-2 downregulate Xslu and upregulate the neural plate NCAM, smaller amounts of these mRNAs activate expression of eIF4AII and Xslu and suppress expression of epidermal keratin in animal cap assays. Ectopic expression of eIF4AII mRNA also upregulates transcription of the PKCα and β genes. The sensitivity of the upregulation of neurectodermal markers to GF109203X indicates that the activity of a calcium activated protein kinase C (PKC) is also required. Furthermore ectopic expression of mouse eIF4AII mRNA upregulates the endogenous eIF4AII gene by a process that requires the activity of PKC. The effects of eIF4AII appear to be direct as conditional expression of eIF4AII in animal cap explants at the equivalent of stage 11.5 induces the endogenous eIF4AII and neural fold genes within 40 minutes. Expression of eIF4AII and activation of PKC sensitizes the embryonic ectoderm to the neuralising effect of noggin. We suggest that in developing embryos the neuralizing signal emanating from the organiser at first induces eIF4AII and the prospective neural crest in an arc low on the dorsal aspect of the embryo. As the neuralizing signal increases in intensity close to the organizer region, the tissue becomes committed to a neural plate phenotype. Expression of Xash3A may suppress further expression of neural plate border genes within the prospective neural plate thereby subdividing the neurectoderm into two distinct regions.
Serrate-mediated activation of Notch is specifically blocked by the product of the gene fringe in the dorsal compartment of the Drosophila wing imaginal disc
Authors: Fleming Robert J. , Gu Yi , Hukriede Neil A. 
Published: April 2021

ABSTRACT
In the developing imaginal wing disc of Drosophila, cells at the dorsoventral boundary require localized Notch activity for specification of the wing margin. The Notch ligands Serrate and Delta are required on opposite sides of the presumptive wing margin and, even though activated forms of Notch generate responses on both sides of the dorsoventral boundary, each ligand generates a compartment-specific response. In this report we demonstrate that Serrate, which is expressed in the dorsal compartment, does not signal in the dorsal regions due to the action of the fringe gene product. Using ectopic expression, we show that regulation of Serrate by fringe occurs at the level of protein and not Serrate transcription. Furthermore, replacement of the N-terminal region of Serrate with the corresponding region of Delta abolishes the ability of fringe to regulate Serrate without altering Serrate-specific signaling.
Archenteron precursor cells can organize secondary axial structures in the sea urchin embryo
Authors: Benink Hélène , Wray Gregory , Hardin Jeff 
Published: April 2021

ABSTRACT
Local cell-cell signals play a crucial role in establishing major tissue territories in early embryos. The sea urchin embryo is a useful model system for studying these interactions in deuterostomes. Previous studies showed that ectopically implanted micromeres from the 16-cell embryo can induce ectopic guts and additional skeletal elements in sea urchin embryos. Using a chimeric embryo approach, we show that implanted archenteron precursors differentiate autonomously to produce a correctly proportioned and patterned gut. In addition, the ectopically implanted presumptive archenteron tissue induces ectopic skeletal patterning sites within the ectoderm. The ectopic skeletal elements are bilaterally symmetric, and flank the ectopic archenteron, in some cases resulting in mirror-image, symmetric skeletal elements. Since the induced patterned ectoderm and supernumerary skeletal elements are derived from the host, the ectopic presumptive archenteron tissue can act to ‘organize’ ectopic axial structures in the sea urchin embryo.
The role of Paraxial Protocadherin in selective adhesion and cell movements of the mesoderm during Xenopus gastrulation
Authors: Kim Sung-Hyun , Yamamoto Akihito , Bouwmeester Tewis , Agius Eric , De Robertis E. M. 
Published: April 2021

ABSTRACT
Paraxial Protocadherin (PAPC) encodes a transmembrane protein expressed initially in Spemann’s organizer and then in paraxial mesoderm. Together with another member of the protocadherin family, Axial Protocadherin (AXPC), it subdivides gastrulating mesoderm into paraxial and axial domains. PAPC has potent homotypic cell adhesion activity in cell dissociation and reaggregation assays. Gain- and loss-of-function microinjection studies indicate that PAPC plays an important role in the convergence and extension movements that drive Xenopus gastrulation. Thus, PAPC is not only an adhesion molecule but also a component of the machinery that drives gastrulation movements in Xenopus. PAPC may provide a link between regulatory genes in Spemann’s organizer and the execution of cell behaviors during morphogenesis.
The RXRα ligand-dependent activation function 2 (AF-2) is important for mouse development
Authors: Mascrez Bénédicte , Mark Manuel , Dierich Andrée , Ghyselinck Norbert B. , Kastner Philippe , Chambon Pierre 
Published: April 2021

ABSTRACT
We have engineered a mouse mutation that specifically deletes the C-terminal 18 amino acid sequence of the RXRα protein. This deletion corresponds to the last helical α structure (H12) of the ligand-binding domain (LBD), and includes the core of the Activating Domain of the Activation Function 2 (AF-2 AD core) that is thought to be crucial in mediating ligand-dependent transactivation by RXRα. The homozygous mutants (RXRαaf2o), which die during the late fetal period or at birth, exhibit a subset of the abnormalities previously observed in RXRα−/− mutants, often with incomplete penetrance. In marked contrast, RXRαaf2o/RXRβ−/− and RXRαaf2o/RXRβ−/−/RXRγ−/− compound mutants display a large array of malformations, which nearly recapitulate the full spectrum of the defects that characterize the fetal vitamin A-deficiency (VAD) syndrome and were previously found in RAR single and compound mutants, as well as in RXRα/RAR(α, β or γ) compound mutants. Analysis of RXRαaf2o/RAR(α, β or γ) compound mutants also revealed that they exhibit many of the defects observed in the corresponding RXRα/RAR compound mutants. Together, these results demonstrate the importance of the integrity of RXR AF-2 for the developmental functions mediated by RAR/RXR heterodimers, and hence suggest that RXR liganddependent transactivation is instrumental in retinoid signalling during development.
Cell type-specific regulation of the Drosophila FMRF-NH
2 neuropeptide gene by Apterous, a LIM homeodomain transcription factor
Authors: Benveniste Ronald J. , Thor Stefan , Thomas John B. , Taghert Paul H. 
Published: April 2021

ABSTRACT
We describe the direct and cell-specific regulation of the Drosophila FMRFa neuropeptide gene by Apterous, a LIM homeodomain transcription factor. dFMRFa and Apterous are expressed in partially overlapping subsets of neurons, including two of the seventeen dFMRFa cell types, the Tv neuroendocrine cells and the SP2 interneurons. Apterous contributes to the initiation of dFMRFa expression in Tv neurons, but not in those dFMRFa neurons that do not express Apterous. Apterous is not required for Tv neuron survival or morphological differentiation. Apterous contributes to the maintenance of dFMRFa expression by postembryonic Tv neurons, although the strength of its regulation is diminished. Apterous regulation of dFMRFa expression includes direct mechanisms, although ectopic Apterous does not induce ectopic dFMRFa. These findings show that, for a subset of neurons that share a common neurotransmitter phenotype, the Apterous LIM homeoprotein helps define neurotransmitter expression with very limited effects on other aspects of differentiation.
Regulation of EGF receptor signaling establishes pattern across the developing Drosophila retina
Authors: Spencer Susan A. , Powell Patricia A. , Miller David T. , Cagan Ross L. 
Published: April 2021

ABSTRACT
SUMMARY
Developing epithelia use a variety of patterning mechanisms to place individual cells into their correct positions. However, the means by which pattern elements are established are poorly understood. Here, we report evidence that regulation of Drosophila EGF receptor (DER) activity plays a central role in propagating the evenly spaced array of ommatidia across the developing Drosophila retina. DER activity is essential for establishing the first ommatidial cell fate, the R8 photoreceptor neuron. R8s in turn appear to signal through Rhomboid and Vein to create a patterned array of ‘proneural clusters’ which contain high levels of phosphorylated ERKA and the bHLH protein Atonal. Finally, secretion by the proneural clusters of Argos represses DER activity in less mature regions to create a new pattern of R8s. Propagation of this process anteriorly results in a retina with a precise array of maturing ommatidia.
The specification of sympathetic neurotransmitter phenotype depends on gp130 cytokine receptor signaling
Authors: Geissen Markus , Heller Stefan , Pennica Diane , Ernsberger Uwe , Rohrer Hermann 
Published: April 2021

ABSTRACT
Sympathetic ganglia are composed of noradrenergic and cholinergic neurons. The differentiation of cholinergic sympathetic neurons is characterized by the expression of choline acetyltransferase (ChAT) and vasoactive intestinal peptide (VIP), induced in vitro by a subfamily of cytokines, including LIF, CNTF, GPA, OSM and cardiotrophin-1 (CT-1). To interfere with the function of these neuropoietic cytokines in vivo, antisense RNA for gp130, the common signal-transducing receptor subunit for neuropoietic cytokines, was expressed in chick sympathetic neurons, using retroviral vectors. A strong reduction in the number of VIP-expressing cells, but not of cells expressing ChAT or the adrenergic marker tyrosine hydroxylase (TH), was observed. These results reveal a physiological role of neuropoietic cytokines for the control of VIP expression during the development of cholinergic sympathetic neurons.
Dynamic changes in the functions of Odd-skipped during early Drosophila embryogenesis
Authors: Dréan Benedicte Saulier-Le , Nasiadka Andrzej , Dong Jianli , Krause Henry M. 
Published: April 2021

ABSTRACT
Although many of the genes that pattern the segmented body plan of the Drosophila embryo are known, there remains much to learn in terms of how these genes and their products interact with one another. Like many of these gene products, the protein encoded by the pair-rule gene odd-skipped (Odd) is a DNA-binding transcription factor. Genetic experiments have suggested several candidate target genes for Odd, all of which appear to be negatively regulated. Here we use pulses of ectopic Odd expression to test the response of these and other segmentation genes. The results are complex, indicating that Odd is capable of repressing some genes wherever and whenever Odd is expressed, while the ability to repress others is temporally or spatially restricted. Moreover, one target gene, fushi tarazu, is both repressed and activated by Odd, the outcome depending upon the stage of development. These results indicate that the activity of Odd is highly dependent upon the presence of cofactors and/or overriding inhibitors. Based on these results, and the segmental phenotypes generated by ectopic Odd, we suggest a number of new roles for Odd in the patterning of embryonic segments. These include gap-, pair-rule- and segment polarity-type functions.
decapentaplegic is required for arrest in G1 phase during Drosophila eye development
Authors: Horsfield Julie , Penton Andrea , Secombe Julie , Hoffman F. Michael , Richardson Helena 
Published: April 2021

ABSTRACT
During eye development in Drosophila, cell cycle progression is coordinated with differentiation. Prior to differentiation, cells arrest in G1 phase anterior to and within the morphogenetic furrow. We show that Decapentaplegic (Dpp), a TGF-β family member, is required to establish this G1 arrest, since Dpp-unresponsive cells located in the anterior half of the morphogenetic furrow show ectopic S phases and ectopic expression of the cell cycle regulators Cyclins A, E and B. Conversely, ubiquitous over-expression of Dpp in the eye imaginal disc transiently inhibits S phase without affecting Cyclin E or Cyclin A abundance. This Dpp-mediated inhibition of S phase occurs independently of the Cyclin A inhibitor Roughex and of the expression of Dacapo, a Cyclin E-Cdk2 inhibitor. Furthermore, Dpp-signaling genes interact genetically with a hypomorphic cyclin E allele. Taken together our results suggest that Dpp acts to induce G1 arrest in the anterior part of the morphogenetic furrow by a novel inhibitory mechanism. In addition, our results provide evidence for a Dpp-independent mechanism that acts in the posterior part of the morphogenetic furrow to maintain G1 arrest.
Dorsoventral patterning in the Drosophila retina by wingless
Authors: Heberlein Ulrike , Borod Emily R. , Chanut Françoise A. 
Published: April 2021

ABSTRACT
The eye imaginal disc displays dorsal-ventral (D-V) and anterior-posterior polarity prior to the onset of differentiation, which initiates at the intersection of the D-V midline with the posterior margin. As the wave of differentiation progresses anteriorly, additional asymmetry develops as ommatidial clusters rotate coordinately in opposite directions in the dorsal and ventral halves of the disc; this forms a line of mirror-image symmetry, the equator, which coincides with the D-V midline of the disc. How D-V pattern is established and how it relates to ommatidial rotation are unknown. Here we address this question by assaying the expression of various asymmetric markers under conditions that lead to ectopic differentiation, such as removal of patched or wingless function. We find that D-V patterning develops gradually and that wingless plays an important role in setting up this pattern. We show that wingless is necessary and sufficient to induce dorsal expression of the gene mirror prior to the start of differentiation and also to restrict the expression of the WR122 marker to differentiating photoreceptors near the equator. In addition, we find that manipulations in wingless expression shift the D-V axis of the disc as evidenced by changes in the expression domains of asymmetric markers, the position of the site of initiation and the equator, and the pattern of epithelial growth. Thus, Wg appears to coordinately regulate multiple events related to D-V patterning in the developing retina.
MASH1 activates expression of the paired homeodomain transcription factor Phox2a, and couples pan-neuronal and subtype-specific components of autonomic neuronal identity
Authors: Lo Liching , Tiveron Marie-Catherine , Anderson David J. 
Published: April 2021

ABSTRACT
We have investigated the genetic circuitry underlying the determination of neuronal identity, using mammalian peripheral autonomic neurons as a model system. Previously, we showed that treatment of neural crest stem cells (NCSCs) with bone morphogenetic protein-2 (BMP-2) leads to an induction of MASH1 expression and consequent autonomic neuronal differentiation. We now show that BMP2 also induces expression of the paired homeodomain transcription factor Phox2a, and the GDNF/NTN signalling receptor tyrosine kinase c-RET. Constitutive expression of MASH1 in NCSCs from a retroviral vector, in the absence of exogenous BMP2, induces expression of both Phox2a and c-RET in a large fraction of infected colonies, and also promotes morphological neuronal differentiation and expression of pan-neuronal markers. In vivo, expression of Phox2a in autonomic ganglia is strongly reduced in Mash1 −/− embryos. These loss- and gain-of-function data suggest that MASH1 positively regulates expression of Phox2a, either directly or indirectly. Constitutive expression of Phox2a, by contrast to MASH1, fails to induce expression of neuronal markers or a neuronal morphology, but does induce expression of c-RET. These data suggest that MASH1 couples expression of pan-neuronal and subtype-specific components of autonomic neuronal identity, and support the general idea that identity is established by combining subprograms involving cascades of transcription factors, which specify distinct components of neuronal phenotype.
Identification of genes controlling germ cell migration and embryonic gonad formation in Drosophila
Authors: Moore Lisa A. , Broihier Heather Tarczy , Doren Mark Van , Lunsford Lynn B. , Lehmann Ruth 
Published: April 2021

ABSTRACT
Gonadogenesis in the Drosophila embryo is a complex process involving numerous cellular migratory steps and cell-cell interactions. The mechanisms guiding germ cells to move through, recognize and adhere to specific cell types are poorly understood. In order to identify genes that are required for these processes, we have conducted an extensive mutagenesis of the third chromosome and screened for mutations disrupting germ cell migration at any point in embryonic development. Phenotypic analysis of these mutants demonstrates that germ cell migration can be broken down into discrete developmental steps, with each step requiring a specific set of genes. Many of these genes are involved in the development of gonadal mesoderm, the tissue that associates with germ cells to form the embryonic gonad. Moreover, mutations that we isolated affecting embryonic patterning as well as germ cell migration suggest that the origin of gonadal mesoderm lies within the eve domain of the developing mesoderm.
A common precursor for hematopoietic and endothelial cells
Authors: Choi Kyunghee , Kennedy Marion , Kazarov Alexander , Papadimitriou John C. , Keller Gordon 
Published: April 2021

ABSTRACT
Embryonic stem cell-derived embryoid bodies contain a unique precursor population which, in response to vascular endothelial growth factor, gives rise to blast colonies in semi-solid medium. Upon transfer to liquid culture with appropriate cytokines, these blast colonies generate both hematopoietic and adherent, stromal-type cells. Cells within the adherent population display characteristics of endothelial lineage including the expression of CD31, flk-1, flt-1, tie-2, the capacity to take up acetylated LDL and the presence of cytoplasmic Weibel-Palade bodies. Mixing studies demonstrated that the hematopoietic and endothelial precursors within the blast colonies develop from the same cell, the blast colony-forming cell. Kinetic analysis showed that the blast colony-forming cell represents a transient cell population that develops early and is lost quickly during embryoid body development. These findings provide strong evidence that the blast colony-forming cell represents the long-hypothesized hemangioblast, the common precursor of the hematopoietic and endothelial lineages.
Functional analysis of eve stripe 2 enhancer evolution in Drosophila: rules governing conservation and change
Authors: Ludwig Michael Z. , Patel Nipam H. , Kreitman Martin 
Published: April 2021

ABSTRACT
Experimental investigations of eukaryotic enhancers suggest that multiple binding sites and trans-acting regulatory factors are often required for wild-type enhancer function. Genetic analysis of the stripe 2 enhancer of even-skipped (eve), an important developmental gene in Drosophila, provides support for this view. Given the importance of even-skipped expression in early Drosophila development, it might be predicted that many structural features of the stripe 2 enhancer will be evolutionarily conserved, including the DNA sequences of protein binding sites and the spacing between them.
To test this hypothesis, we compared sequences of the stripe 2 enhancer between four species of Drosophila: D. melanogaster, D. yakuba, D. erecta and D. pseudoobscura. Our analysis revealed a large number of nucleotide substitutions in regulatory protein binding sites for bicoid, hunchback, Kruppel and giant, as well as a systematic change in the size of the enhancer. Some of the binding sites in D. melanogaster are either absent or modified in other species. One functionally important bicoid-binding site in D. melanogaster appears to be recently evolved.
We, therefore, investigated possible functional consequences of sequence differences among these stripe 2 enhancers by P-element-mediated transformation. This analysis revealed that the eve stripe 2 enhancer from each of the four species drove reporter gene expression at the identical time and location in D. melanogaster embryos. Double staining of native eve protein and transgene mRNA in early embryos showed that the reporter gene mimicked native eve expression and, in every case, produced sharply defined stripes at the blastoderm stage that were coincident with eve stripe 2 protein.
We argue that stripe 2 eve expression in Drosophila evolution can be viewed as being under constant stabilizing selection with respect to the location of the anterior and posterior borders of the stripe. We further hypothesize that the stripe 2 enhancer is functionally robust, so that its evolution may be governed by the fixation of both slightly deleterious and adaptive mutations in regulatory protein binding sites as well as in the spacing between binding sites. This view allows for a slow but continual turnover of functionally important changes in the stripe 2 enhancer.
Hoxa1 and Hoxb1 synergize in patterning the hindbrain, cranial nerves and second pharyngeal arch
Authors: Gavalas Anthony , Studer Michèle , Lumsden Andrew , Rijli Filippo M. , Krumlauf Robb , Chambon Pierre 
Published: April 2021

ABSTRACT
The analysis of Hoxa1 and Hoxb1 null mutants suggested that these genes are involved in distinct aspects of hindbrain segmentation and specification. Here we investigate the possible functional synergy of the two genes. The generation of Hoxa13′RARE/Hoxb13′RARE compound mutants resulted in mild facial motor nerve defects reminiscent of those present in the Hoxb1 null mutants. Strong genetic interactions between Hoxa1 and Hoxb1 were uncovered by introducing the Hoxb13′RARE and Hoxb1 null mutations into the Hoxa1 null genetic background. Hoxa1null/Hoxb13′RARE and Hoxa1null/Hoxb1null double homozygous embryos showed additional patterning defects in the r4-r6 region but maintained a molecularly distinct r4-like territory. Neurofilament staining and retrograde labelling of motor neurons indicated that Hoxa1 and Hoxb1 synergise in patterning the VIIth through XIth cranial nerves. The second arch expression of neural crest cell markers was abolished or dramatically reduced, suggesting a defect in this cell population. Strikingly, the second arch of the double mutant embryos involuted by 10.5 dpc and this resulted in loss of all second arch-derived elements and complete disruption of external and middle ear development. Additional defects, most notably the lack of tympanic ring, were found in first arch-derived elements, suggesting that interactions between first and second arch take place during development. Taken together, our results unveil an extensive functional synergy between Hoxa1 and Hoxb1 that was not anticipated from the phenotypes of the simple null mutants.