bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidermal induction and inhibition of neural fate by translation initiation factor 4AIII
Authors: Weinstein Daniel C. , Honoré Eric , Hemmati-Brivanlou Ali 
Published: April 2021

ABSTRACT
Bone Morphogenetic Protein-4 (BMP-4) is a potent epidermal inducer and inhibitor of neural fate. We have used differential screening to identify genes involved in epidermal induction downstream of BMP-4 and report here evidence of a novel translational mechanism that regulates the division of the vertebrate ectoderm into regions of neural and epidermal fate. In dissociated Xenopus ectoderm, addition of ectopic BMP-4 leads to an increase in the expression of translation initiation factor 4AIII (eIF-4AIII), a divergent member of the eIF-4A gene family until now characterized only in plants. In the gastrula embryo XenopuseIF-4AIII (XeIF-4AIII) expression is elevated in the ventral ectoderm, a site of active BMP signal transduction. Moreover, overexpression of XeIF-4AIII induces epidermis in dissociated cells that would otherwise adopt a neural fate, mimicking the effects of BMP-4. Epidermal induction by XeIF-4AIII requires both an active BMP signaling pathway and an extracellular intermediate. Our results suggest that XeIF-4AIII can regulate changes in cell fate through selective mRNA translation. We propose that BMPs and XeIF-4AIII interact through a positive feedback loop in the ventral ectoderm of the vertebrate gastrula.
Notochord to endoderm signaling is required for pancreas development
Authors: Kim Seung K. , Hebrok Matthias , Melton Douglas A. 
Published: April 2021

ABSTRACT
The role of the notochord in inducing and patterning adjacent neural and mesodermal tissues is well established. We provide evidence that the notochord is also required for one of the earliest known steps in the development of the pancreas, an endodermally derived organ. At a developmental stage in chick embryos when the notochord touches the endoderm, removal of notochord eliminates subsequent expression of several markers of dorsal pancreas bud development, including insulin, glucagon and carboxypeptidase A. Pancreatic gene expression can be initiated and maintained in prepancreatic chick endoderm grown in vitro with notochord. Non-pancreatic endoderm, however, does not express pancreatic genes when recombined with the same notochord. The results suggest that the notochord provides a permissive signal to endoderm to specify pan-creatic fate in a stepwise manner.
A role for FGF-8 in the dorsoventral patterning of the zebrafish gastrula
Authors: Fürthauer Maximilian , Thisse Christine , Thisse Bernard 
Published: April 2021

ABSTRACT
Signals released from Spemann’s organizer, together with ventralizing factors such as BMPs, are necessary to pattern the dorsoventral axis of the vertebrate embryo. We report that a member of the FGF family, fgf-8, not secreted by the axial mesoderm but expressed in a dorsoventral gradient at the margin of the zebrafish gastrula, also contributes to the establishment of the dorsoventral axis of the embryo. Ectopic expression of FGF-8 leads to the expansion of dorsolateral derivatives at the expense of ventral and posterior domains. Moreover, FGF-8 displays some organizer properties as it induces the formation of a partial secondary axis in the absence of factors released from Spemann’s organizer territory. Analysis of its interaction with the ventralizing factors, BMPs, reveals that overexpression of FGF-8 inhibits the expression of these factors in the ventral part of the embryo as early as blastula stage, suggesting that FGF8 acts upstream of BMP2 and BMP4. We conclude that FGF-8 is involved in defining dorsoventral identity and is an important organizing factor responsible for specification of mesodermal and ectodermal dorsolateral territories of the zebrafish gastrula.
Suppressor of Hairless-independent events in Notch signaling imply novel pathway elements
Authors: Matsuno Kenji , Go Masahiro J. , Sun Xin , Eastman Deborah S. , Artavanis-Tsakonas Spyros 
Published: April 2021

ABSTRACT
The Notch (N) pathway defines an evolutionarily conserved cell signaling mechanism that governs cell fate choices through local cell interactions. The ankyrin repeat region of the Notch receptor is essential for signaling and has been implicated in the interactions between Notch and two intra-cellular elements of the pathway: Deltex (Dx) and Sup-pressor of Hairless (Su(H)). Here we examine directly the function of the Notch cdc10/ankyrin repeats (ANK repeats) by transgenic and biochemical analysis. We present evidence implicating the ANK repeats in the regulation of Notch signaling through homotypic interactions. In vivo expression of the Notch ANK repeats reveals a cell non-autonomous effect and elicits mutant phenotypes that indicate the existence of novel downstream events in Notch signaling. These signaling activities are independent of the known effector Su(H) and suggest the existence of yet unidentified Notch pathway components.
The terminal differentiation factor LIN-29 is required for proper vulval morphogenesis and egg laying in Caenorhabditis elegans
Authors: Bettinger Jill C. , Euling Susan , Rougvie Ann E. 
Published: April 2021

ABSTRACT
Caenorhabditis elegans vulval development culminates during exit from the L4-to-adult molt with the formation of an opening through the adult hypodermis and cuticle that is used for egg laying and mating. Vulva formation requires the heterochronic gene lin-29, which triggers hypodermal cell terminal differentiation during the final molt. lin-29 mutants are unable to lay eggs or mate because no vulval opening forms; instead, a protrusion forms at the site of the vulva. We demonstrate through analysis of genetic mosaics that lin-29 is absolutely required in a small subset of lateral hypodermal seam cells, adjacent to the vulva, for wild-type vulva formation and egg laying. However, lin-29 function is not strictly limited to the lateral hypodermis. First, LIN-29 accumulates in many non-hypodermal cells with known roles in vulva formation or egg laying. Second, animals homozygous for one lin-29 allele, ga94, have the vulval defect and cannot lay eggs, despite having a terminally differentiated adult lateral hypodermis. Finally, vulval morphogenesis and egg laying requires lin-29 activity within the EMS lineage, a lineage that does not generate hypodermal cells.
A silencer is required for maintenance of transcriptional repression throughout Drosophila development
Authors: Busturia Ana , Wightman Christopher D. , Sakonju Shigeru 
Published: April 2021

ABSTRACT
Transcriptional silencing by the Polycomb Group of genes maintains the position-specific repression of homeotic genes throughout Drosophila development. The Polycomb Group of genes characterized to date encode chromatinassociated proteins that have been suggested to form heterochromatin-like structures. By studying the expression of reporter genes, we have identified a 725 bp fragment, called MCP725, in the homeotic gene Abdominal-B, that accurately maintains position-specific silencing during proliferation of imaginal cells. Silencing by MCP725 requires the Polycomb and the Polycomblike genes, indicating that it contains a Polycomb response element. To investigate the mechanisms of transcriptional silencing by MCP725, we have studied its temporal requirements by removing MCP725 from the transgene at various times during development. We have discovered that excision of MCP725 during larval stages leads to loss of silencing. Our findings indicate that the silencer is required for the maintenance of the repressed state throughout cell proliferation. They also suggest that propagation of the silenced state does not occur merely by templating of a heterochromatin structure by virtue of protein-protein interactions. Rather, they suggest that silencers play an active role in the maintenance of the position-specific repression throughout development.
bag-of-marbles and benign gonial cell neoplasm act in the germline to restrict proliferation during Drosophila spermatogenesis
Authors: Gönczy Pierre , Matunis Erika , DiNardo Stephen 
Published: April 2021

ABSTRACT
Stem cells divide asymmetrically, regenerating a parental stem cell and giving rise to a daughter cell with a distinct fate. In many stem cell lineages, this daughter cell undergoes several amplificatory mitoses, thus generating more cells that embark on the differentiation program specific for the given lineage. Spermatogenesis in Drosophila is a model system to identify molecules regulating stem cell lineages. Mutations at two previously identified loci, bag-of-marbles (bam) and benign gonial cell neoplasm (bgcn), prevent progression through spermatogenesis and oogenesis, resulting in the overproliferation of undifferentiated germ cells. Here we investigate how bam and bgcn regulate the male germline stem cell lineage. By generating FLP-mediated clones, we demonstrate that both bam and bgcn act autonomously in the germline to restrict proliferation during spermatogenesis. By using enhancer trap lines, we find that the overproliferating germ cells express markers specific to amplifying germ cells, while at the same time retaining the expression of some markers of stem cell and primary spermatogonial cell fate. However, we find that germ cells accumulating in bam or bgcn mutant testes most resemble amplifying germ cells, because they undergo incomplete cytokinesis and progress through the cell cycle in synchrony within a cyst, which are two characteristics of amplifying germ cells, but not of stem cells. Taken together, our results suggest that bam and bgcn regulate progression through the male germline stem cell lineage by cell-intrinsically restricting the proliferation of amplifying germ cells.
Targeted disruption of Hoxd-10 affects mouse hindlimb development
Authors: Carpenter Ellen M. , Goddard Judy M. , Davis Allan P. , Nguyen T. Paul , Capecchi Mario R. 
Published: April 2021

ABSTRACT
Targeted disruption of the Hoxd-10 gene, a 5′ member of the mouse HoxD linkage group, produces mice with hindlimb-specific defects in gait and adduction. To determine the underlying causes of this locomotor defect, mutant mice were examined for skeletal, muscular and neural abnormalities. Mutant mice exhibit alterations in the vertebral column and in the bones of the hindlimb. Sacral vertebrae beginning at the level of S2 exhibit homeotic transformations to adopt the morphology of the next most anterior vertebra. In the hindlimb, there is an anterior shift in the position of the patella, an occasional production of an anterior sesamoid bone, and an outward rotation of the lower part of the leg, all of which contribute to the defects in locomotion. No major alterations in hindlimb musculature were observed, but defects in the nervous system were evident. There was a decrease in the number of spinal segments projecting nerve fibers through the sacral plexus to innervate the musculature of the hindlimb. Deletion of a hindlimb nerve was seen in some animals, and a shift was evident in the position of the lumbar lateral motor column. These observations suggest a role for the Hoxd-10 gene in establishing regional identity within the spinal cord and imply that patterning of the spinal cord may have intrinsic components and is not completely imposed by the surrounding mesoderm.
Linking Frizzled and Wnt signaling in Drosophila development
Authors: Tomlinson Andrew , Strapps Walter R. , Heemskerk Jill 
Published: April 2021

ABSTRACT
Drosophila Frizzled-2 (Dfz2) has been identified as a putative fly Wingless (Wg) receptor. Although Dfz2 shows significant homology with Fz, a protein that operates in the mechanisms that establish planar polarity in Drosophila epithelia, any clear evidence for an involvement by Fz in a Wnt signaling pathway has hitherto been absent. Here we describe the planar polarity phenotypes of loss-of-function and overexpression of Fz in the developing Drosophila eye and find it almost identical to the loss-of-function or over-expression of Dishevelled (Dsh – a protein operating in Wnt second messenger systems). In addition, we show that over-expression of Shaggy (Sgg – another component of the Wnt pathway) in the eye also causes a phenotype similar to Fz and Dsh. To test further the link between planar polarity and Wnt signaling we misexpressed Wg in the developing eye and found it had a potent polarizing effect in the retinal epithelium. Since the overexpression of Fz in the developing eye gave a phenotype consistent with activating the Wnt pathway, we tested overexpression of Fz in the developing embryonic ectoderm and found that it phenocopied over-expression of Wg. To check that Fz was indeed able to activate a Wnt pathway we overexpressed it in Drosophila tissue culture cells and observed the characteristic phosphorylation of Dsh that occurs in response to Wnt signaling. Taken together our results significantly strengthen the case for Fz acting in a Wnt signaling pathway in Drosophila.
Dorso-ventral ectodermal compartments and origin of apical ectodermal ridge in developing chick limb
Authors: Altabef Muriel , Clarke Jonathan D. W. , Tickle Cheryll 
Published: April 2021

ABSTRACT
We wish to understand how limbs are positioned with respect to the dorso-ventral axis of the body in vertebrate embryos, and how different regions of limb bud ectoderm, i.e. dorsal ectoderm, apical ridge and ventral ectoderm, originate. Signals from dorsal and ventral ectoderm control dorso-ventral patterning while the apical ectodermal ridge (AER) controls bud outgrowth and patterning along the proximo-distal axis. We show, using cell-fate tracers, the existence of two distinct ectodermal compartments, dorsal versus ventral, in both presumptive limb and flank of early chick embryos. This organisation of limb ectoderm is the first direct evidence, in vertebrates, of compartments in non-neural ectoderm. Since the apical ridge appears to be confined to this compartment boundary, this positions the limb. The mesoderm, unlike the ectoderm, does not contain two separate dorsal and ventral cell lineages, suggesting that dorsal and ventral ectoderm compartments may be important to ensure appropriate control of mesodermal cell fate. Surprisingly, we also show that cells which form the apical ridge are initially scattered in a wide region of early ectoderm and that both dorsal and ventral ectoderm cells contribute to the apical ridge, intermingling to some extent within it.
A novel α integrin subunit associates with β PS and functions in tissue morphogenesis and movement during Drosophila development
Authors: Stark Karen A. , Yee Gene H. , Roote Carol E. , Williams Erin L. , Zusman Susan , Hynes Richard O. 
Published: April 2021

ABSTRACT
We have identified a novel a integrin subunit in Drosophila, that associates with bPS integrin. We report the temporal expression of the gene encoding this integrin subunit, which we have called aPS3, throughout development and the localization of its expression during embryogenesis. aPS3 RNA was localized to tissues undergoing invagination, tissue movement and morphogenesis such as salivary gland, trachea, midgut, dorsal vessel, midline of the ventral nerve cord, amnioserosa and the amnioproctodeal invagination. aPS3 DNA localized to the chromosomal vicinity of scab (scb), previously identified by a failure of dorsal closure. Embryos homozygous for the l19 allele of scb had no detectable aPS3 RNA and the 1035 allele of scb contains a P element inserted just 5¢ of the coding region for the shorter of the gene’s two transcripts. Furthermore, mutations in the scb locus exhibit additional defects corresponding to sites of aPS3 transcription, including abnormal salivary glands, mislocalization of the pericardial cells and interrupted trachea. Removal of both maternal and zygotic bPS produced similar defects, indicating that these two integrin subunits associate in vivo and function in the movement and morphogenesis of tissues during development in Drosophila. Phenotypic similarities suggest that laminin A is a potential ligand for this integrin, at least in some tissues.
SpMyb functions as an intramodular repressor to regulate spatial expression of Cyllla in sea urchin embryos
Authors: Coffman James A. , Kirchhamer Carmen V. , Harrington Michael G. , Davidson Eric H. 
Published: April 2021

ABSTRACT
The Cyllla actin gene of Strongylocentrotus purpuratus is transcribed exclusively in the embryonic aboral ectoderm, under the control of 2.3 kb cis-regulatory domain that contains a proximal module that controls expression in early embryogenesis, and a middle module that controls expression in later embryogenesis. Previous studies demonstrated that the SpRunt-1 target site within the middle module is required for the sharp increase in Cyllla transcription which accompanies differentiation of the aboral ectoderm, and that a negative regulatory region near the SpRunt-1 target site is required to prevent ectopic transcription in the oral ectoderm and skeletogenic mesenchyme. This negative regulatory region contains a consensus binding site for the myb family of transcription factors. In vitro DNA-binding experiments reveal that a protein in blastula-stage nuclei interacts specifically with the myb target site. Gene transfer experiments utilizing Cyllla reporter constructs containing oligonucleotide substitutions indicate that this site is both necessary and sufficient to prevent ectopic expression of Cyllla. Synthetic oligonucleotides containing the myb target site were used to purify a protein from sea urchin embryo nuclear extracts by affinity chromatography. This protein is immunoprecipitated by antibodies specific to the evolutionarily conserved myb domain, and amino acid sequences obtained from the purified protein were found to be identical to sequences within the myb domain. Sequence information was used to obtain cDNA clones of SpMyb, the S. purpura-tus member of the myb family of transcription factors. Through interactions within the middle module, SpMyb functions to repress activation of Cyllla in the oral ectoderm and skeletogenic mesenchyme.
Vitamin A deficiency and mutations of RXRα, RXRβ and RARα lead to early differentiation of embryonic ventricular cardiomyocytes
Authors: Kastner Philippe , Messaddeq Nadia , Mark Manuel , Wendling Olivia , Grondona Jesus M. , Ward Simon , Ghyselinck Norbert , Chambon Pierre 
Published: April 2021

ABSTRACT
Knock-out of the mouse RXRa gene was previously shown to result in a hypoplastic heart ventricular wall, histologically detectable in 12.5 dpc fetuses. We show here that a precocious differentiation can be detected as early as 8.5 dpc in ventricular cardiomyocytes of RXRα−/− mutants. This precocious differentiation, which is characterized by the presence of striated myofibrils, sarcoplasmic reticulum and intercalated disks, is found after 9.5 dpc in about 50% of RXRα−/− subepicardial myocytes. In contrast, wild-type subepicardial myocytes remain morphologically undifferentiated up to at least 16.5 dpc. A similar precocious differentiation was observed in 9.5 dpc subepicardial myocytes of several RXR0α−/− and RARα−/− mutants, as well as in vitamin A-deficient embryos. The proportion of differentiated subepicardial myocytes almost reached 100% in RXRα/RXRβ double null mutants, indicating a partial functional redundancy between RXRα and RXRβ. This differentiation defect was always paralleled by a decrease in the mitotic index. In addition, subepicardial myocytes of RXRα−/−, RXRα−/−1/RXRβ−/− or vitamin A deficient, but not of RXRβ−/− and RARα−/− embryos, were often flattened and more loosely connected to one another than those of WT embryos. Thus, retinoids are required at early stages of cardiac development to prevent differentiation, support cell proliferation and control the shape of ventricular myocytes, and both RXRs and RARs participate in the mediation of these functions.
SUP-17, a Caenorhabditis elegans ADAM protein related to Drosophila KUZBANIAN, and its role in LIN-12/NOTCH signalling
Authors: Wen Chenhui , Metzstein Mark M. , Greenwald Iva 
Published: April 2021

ABSTRACT
LIN-12/NOTCH proteins mediate cell-cell interactions that specify cell fates. Previous work suggested that sup-17 facilitates lin-12 signalling in Caenorhabditis elegans. Here, we show that sup-17 encodes a member of the ADAM family of metalloproteases. SUP-17 is highly similar to Drosophila KUZBANIAN, which functions in Drosophila neurogenesis, and the vertebrate ADAM10 protein. Furthermore, we show by genetic analysis that the extracellular domain of LIN-12 appears to be necessary for sup-17 to facilitate lin-12 signalling and that sup-17 does not act downstream of lin-12. Finally, we show by cell ablation experiments that sup-17 can act cell autonomously to facilitate lin-12 activity. We discuss the implications of our observations for LIN-12/NOTCH signalling and how our results complement and extend results obtained from genetic analysis of kuz in Drosophila.
The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates
Authors: Bonini Nancy M. , Bui Quang T. , Gray-Board Gladys L. , Warrick John M. 
Published: April 2021

ABSTRACT
The fly eyes absent (eya) gene which is essential for compound eye development in Drosophila, was shown to be functionally replaceable in eye development by a vertebrate Eya homolog. The relationship between eya and that of the eyeless gene, a Pax-6 homolog, critical for eye formation in both flies and man, was defined: eya was found to be essential for eye formation by eyeless. Moreover, eya could itself direct ectopic eye formation, indicating that eya has the capacity to function as a master control gene for eye formation. Finally, we show that eya and eyeless together were more effective in eye formation than either gene alone. These data indicate conservation of the pathway of eya function between flies and vertebrates; they suggest a model whereby eya/Eya gene function is essential for eye formation by eyeless/Pax-6, and that eya/Eya can in turn mediate, via a regulatory loop, the activity of eyeless/Pax-6 in eye formation.
Different levels of Ras activity can specify distinct transcriptional and morphological consequences in early Drosophila embryos
Authors: Greenwood Simon , Struhl Gary 
Published: April 2021

ABSTRACT
The terminal portions of the Drosophila body pattern are specified by the localized activity of the receptor tyrosine kinase Torso (Tor) at each pole of the early embryo. Tor activity elicits the transcription of two ‘gap’ genes, tailless (tll) and huckebein (hkb), in overlapping but distinct domains by stimulating the Ras signal transduction pathway. Here, we show that quantitative variations in the level of Ras activity can specify qualitatively distinct transcriptional and morphological responses. Low levels of Ras activity at the posterior pole direct tll but not hkb transcription; higher levels drive transcription of both genes. Correspondingly, low levels of Ras activity specify a limited subset of posterior terminal structures, whereas higher levels specify a larger subset. However, we also show that the response to Ras activity is not uniform along the body. Instead, levels of Ras activity which suffice to drive tll and hkb transcription at the posterior pole fail to drive their expression in more central portions of the body, apparently due to repression by other gap gene products. We conclude that tll and hkb transcription, as well as the terminal structures, are specified by two inputs: a gradient of Ras activity which emanates from the pole, and the opposing influence of more centrally deployed gap genes which repress the response to Ras.