bluuebunny/crossref_metadata_2025_split huggingface dataset:
A temporal switch in DER signaling controls the specification and differentiation of veins and interveins in the Drosophila wing
Authors: Martín-Blanco Enrique , Roch Fernando , Noll Elizabeth , Baonza Antonio , Duffy Joseph B. , Perrimon Norbert 
Published: April 2021

Abstract
The Drosophila EGF receptor (DER) is required for the specification of diverse cell fates throughout development. We have examined how the activation of DER controls the development of vein and intervein cells in the Drosophila wing. The data presented here indicate that two distinct events are involved in the determination and differentiation of wing cells. (1) The establishment of a positive feedback amplification loop, which drives DER signaling in larval stages. At this time, rhomboid (rho), in combination with vein, initiates and amplifies the activity of DER in vein cells. (2) The late downregulation of DER activity. At this point, the inactivation of MAPK in vein cells is necessary for the maintenance of the expression of decapentaplegic (dpp) and becomes essential for vein differentiation. Together, these temporal and spatial changes in the activity of DER constitute an autoregulatory network that controls the definition of vein and intervein cell types.
mirror controls planar polarity and equator formation through repression of fringe expression and through control of cell affinities
Authors: Yang, Chung-Hui , Simon Michael A. , McNeill Helen 
Published: April 2021

Abstract
The Drosophila eye is divided into dorsal and ventral mirror image fields that are separated by a sharp boundary known as the equator. We have previously demonstrated that Mirror, a homeodomain-containing putative transcription factor with a dorsal-specific expression pattern in the eye, induces the formation of the equator at the boundary between mirror-expressing and non-expressing cells. Here, we provide evidence that suggests mirror regulates equator formation by two mechanisms. First, mirror defines the location of the equator by creating a boundary of fringe expression at the mid-point of the eye. We show that mirror creates this boundary by repressing fringe expression in the dorsal half of the eye. Significantly, a boundary of mirror expression cannot induce the formation of an equator unless a boundary of fringe expression is formed simultaneously. Second, mirror acts to sharpen the equator by reducing the mixing of dorsal and ventral cells at the equator. In support of this model, we show that clones of cells lacking mirror function tend not to mix with surrounding mirror-expressing cells. The tendency of mirror-expressing and non-expressing cells to avoid mixing with each other is not determined by their differences in fringe expression. Thus mirror acts to regulate equator formation by both physically separating the dorsal cells from ventral cells, and restricting the formation of a fng expression boundary to the border where the dorsal and ventral cells meet.
Abrogation of the Cripto gene in mouse leads to failure of postgastrulation morphogenesis and lack of differentiation of cardiomyocytes
Authors: Xu Chunhui , Liguori Giovanna , Persico M. Graziella , Adamson Eileen D. 
Published: April 2021

ABSTRACT
Cripto-1(Cr1) protein encoded by the tdgf1 gene, is a secreted growth factor that is expressed early in embryonic development and is re-expressed in some tumors of the breast and colon. During embryonic development, Cr1 is expressed in inner cell mass cells and the primitive streak, and later is restricted to the developing heart. To investigate the role of Cr1 during mouse development, mice were generated that contain a null mutation of both Cr1 genes, derived from homologous recombination in embryonic stem cells. No homozygous Cr1−/− mice were born, indicating that Cr1 is necessary for embryonic development. Embryos initiated gastrulation and some embryos produced mesoderm up to day E7.5. Increasingly aberrant morphogenesis gave rise to disordered neuroepithelium that failed to produce a recognizable neural tube, or head-fold. Although some biochemical markers of differentiating ectoderm, mesoderm and endoderm were expressed, all the cardiac-specific markers were absent from day E8.7 embryos: αMHC, βMHC, MLC2A, MLC2V and ANF, whereas they were expressed in wild-type embryos. The yolk sac and placental tissues continued development in the absence of the embryo until day E9.5 but lacked large yolk sac blood vessels. Chimeric mice were constructed by microinjection of double targeted Cr1−/− embryonic stem cells into normal C57BL/6 blastocysts. The Cr1 produced by the normal C57BL/6 cells fully rescued the phenotype of Cr1−/− cells, indicating that Cr1 protein acted in a paracrine manner. Cells derived from the embryo proliferated and migrated poorly and had different adhesion properties compared to wild type. Therefore, lethality in the absence of Cr1, likely resulted largely from defective precardiac mesoderm that was unable to differentiate into functional cardiomyocytes.
A gp330/megalin-related protein is required in the major epidermis ofCaenorhabditis elegansfor completion of molting
Authors: Yochem John , Tuck Simon , Greenwald Iva , Han Min 
Published: April 2021

ABSTRACTA genetic analysis of a gp330/megalin-related protein, LRP-1, has been undertaken in Caenorhabditis elegans. Consistent with megalin’s being essential for development of mice, likely null mutations reveal that this large member of the low density lipoprotein receptor family is also essential for growth and development of this nematode. The mutations confer a striking defect, an inability to shed and degrade all of the old cuticle at each of the larval molts. The mutations also cause an arrest of growth usually at the molt from the third to the fourth larval stage. Genetic mosaic analysis suggests that the lrp-1 gene functions in the major epidermal syncytium hyp7, a polarized epithelium that secretes cuticle from its apical surface. Staining of whole mounts with specific monoclonal antibodies reveals that the protein is expressed on the apical surface of hyp7. Sterol starvation can phenocopy the lrp-1 mutations, suggesting that LRP-1 is a receptor for sterols that must be endocytosed by hyp7. These observations indicate that LRP-1 is related to megalin not only structurally but also functionally.
Commissure formation in the embryonic CNS of Drosophila II. Function of the different midline cells
Authors: Hummel, Thomas , Schimmelpfeng Kristina , Klämbt Christian 
Published: April 2021

Abstract
Most of the neurons of the ventral nerve cord send out long projecting axons which cross the midline. In the Drosophila central nervous system (CNS) cells of the midline give rise to neuronal and glial lineages with different functions during the establishment of the commissural pattern. Here we present evidence that beside the previously known NETRIN/FRAZZLED (DCC) signalling system an additional attractive system(s) is operating in the developing embryonic nervous system of Drosophila. Attractive cues appear to be provided by the midline neurons. We show that the glial cells present repulsive signals to the previously described ROUNDABOUT receptor in addition to a permissive contact-dependent signal helping commissural growth cones across the midline. A novel repulsive component is encoded by the karussell gene. Furthermore the midline glial cells separate anterior and posterior commissures. By genetic criteria we demonstrate that some of the genes we have identified are acting in the midline glia whereas other genes are required in the midline neurons. The results lead to a detailed model relating different cellular functions to axonal patterning at the midline.
Head induction in the chick by primitive endoderm of mammalian, but not avian origin
Authors: Knoetgen Hendrik , Viebahn Christoph , Kessel Michael 
Published: April 2021

Abstract
Different types of endoderm, including primitive, definitive and mesendoderm, play a role in the induction and patterning of the vertebrate head. We have studied the formation of the anterior neural plate in chick embryos using the homeobox gene GANF as a marker. GANF is first expressed after mesendoderm ingression from Hensen’s node. We found that, after transplantation, neither the avian hypoblast nor the anterior definitive endoderm is capable of GANF induction, whereas the mesendoderm (young head process, prechordal plate) exhibits a strong inductive potential. GANF induction cannot be separated from the formation of a proper neural plate, which requires an intact lower layer and the presence of the prechordal mesendoderm. It is inhibited by BMP4 and promoted by the presence of the BMP antagonist Noggin. In order to investigate the inductive potential of the mammalian visceral endoderm, we used rabbit embryos which, in contrast to mouse embryos, allow the morphological recognition of the prospective anterior pole in the living, pre-primitive-streak embryo. The anterior visceral endoderm from such rabbit embryos induced neuralization and independent, ectopic GANF expression domains in the area pellucida or the area opaca of chick hosts. Thus, the signals for head induction reside in the anterior visceral endoderm of mammals whereas, in birds and amphibia, they reside in the prechordal mesendoderm, indicating a heterochronic shift of the head inductive capacity during the evolution of mammalia.
The role of dorsoventral interaction in the onset of planarian regeneration
Authors: Kato Kentaro , Orii Hidefumi , Watanabe Kenji , Agata Kiyokazu 
Published: April 2021

Abstract
During planarian regeneration, dorsal and ventral tissues adhere to each other as a result of wound closure. To investigate the role of dorsoventral (DV) interaction in regeneration, dorsal and ventral portions were ectopically reoriented relative to each other by grafting. We sucked a small piece of planarian body into a Pasteur pipette, and then grafted the piece to the original position in DV-reversed orientation. 4 days after grafting, a blastema-like white region was formed on the boundary between the host and the graft. The region grew and formed a cup-shaped projection on both the dorsal and ventral sides of the worm after about 1 week. Histological analysis and in situ hybridization using dorsal and ventral markers revealed that the grafted piece maintained its original DV polarity. Analysis using DV boundary markers clearly indicated that a DV axis was newly established within the projection. Chimeric analysis using a strain-specific marker demonstrated that the projection grew on the DV boundary. Further analysis, using a marker specific for neoblasts and differentiating cells, showed that the projection was composed of neoblasts and/or neoblast-derived cells. Thus, ectopic DV interaction can cause blastema formation, outgrowth and establishment of a DV axis. In addition, staining with tissue- and region-specific markers showed that the projection appears to be identical to the structure from the grafted position to the most anterior or posterior tip. These results suggest that DV interaction evoked by wound closure has a important role in the onset of regeneration, especially for blastema formation and establishment of the DV axis during planarian regeneration.
Extracellular proteolysis alters tooth development in transgenic mice expressing urokinase-type plasminogen activator in the enamel organ
Authors: Zhou Hong-Ming , Nichols Anthony , Wohlwend Annelise , Bolon Isabelle , Vassalli Jean-Dominique 
Published: April 2021

Abstract
By catalyzing plasmin formation, the urokinase-type plasminogen activator (uPA) can generate widespread extracellular proteolysis and thereby play an important role in physiological and pathological processes. Dysregulated expression of uPA during organogenesis may be a cause of developmental defects. Targeted epithelial expression of a uPA-encoding transgene under the control of the keratin type-5 promoter resulted in enzyme production by the enamel epithelium, which does not normally express uPA, and altered tooth development. The incisors of transgenic mice were fragile, chalky-white and, by scanning electron microscopy, their labial surface appeared granular. This phenotype was attributed to a defect in enamel formation during incisor development, resulting from structural and functional alterations of the ameloblasts that differentiate from the labial enamel epithelium. Immunofluorescence revealed that disorganization of the ameloblast layer was associated with a loss of laminin-5, an extracellular matrix molecule mediating epithelial anchorage. Amelogenin, a key protein in enamel formation, was markedly decreased at the enamel-dentin junction in transgenics, presumably because of an apparent alteration in the polarity of its secretion. In addition, increased levels of active transforming growth factor-β could be demonstrated in mandibles of transgenic mice. Since the alterations detected could be attributed to uPA catalytic activity, this model provides evidence as to how dysregulated proteolysis, involving uPA or other extracellular proteases, may have developmental consequences such as those leading to enamel defects.
Delta-1 negatively regulates the transition from prehypertrophic to hypertrophic chondrocytes during cartilage formation
Authors: Crowe Rebecca , Zikherman Julie , Niswander Lee 
Published: April 2021

Abstract
Endochondral bone development begins with the formation of a cartilage template. Chondrocytes within this template undergo a progressive program of maturation from proliferative to prehypertrophic chondrocytes to hypertrophic chondrocytes. The progression of cells through these steps of differentiation must be carefully controlled to ensure coordinated growth. Because the Delta/Notch signaling system is known to regulate cell fate choices, we sought to determine if these molecules might be involved in the progressive cell fate decisions that chondocytes undergo. Here we demonstrate in the chick that Delta/Notch signaling negatively regulates progression from the prehypertrophic to hypertrophic state of differentiation. Delta-1 is expressed specifically in the hypertrophic chondrocytes while Notch-2 is expressed in chondrocytes at all stages. Misexpression of Delta-1 using a replication-competent retrovirus blocks chondrocyte maturation. Prehypertrophic cells form normally but do not undergo differentiation to hypertrophic cells, resulting in shortened skeletal elements that lack ossification. We conclude that Delta-1 acts during chondrogenesis to inhibit the transition from prehypertrophic chondrocytes to hypertrophic chondrocytes, thus defining a novel mechanism for the regulation of the chondrocyte maturation program. In addition, these results reveal a new role for Delta/Notch signaling in regulating the progression to a terminally differentiated state.
Separation of shoot and floral identity in Arabidopsis
Authors: Ratcliffe Oliver J. , Bradley Desmond J. , Coen Enrico S. 
Published: April 2021

ABSTRACT
The overall morphology of an Arabidopsis plant depends on the behaviour of its meristems. Meristems derived from the shoot apex can develop into either shoots or flowers. The distinction between these alternative fates requires separation between the function of floral meristem identity genes and the function of an antagonistic group of genes, which includes TERMINAL FLOWER 1. We show that the activities of these genes are restricted to separate domains of the shoot apex by different mechanisms. Meristem identity genes, such as LEAFY, APETALA 1 and CAULIFLOWER, prevent TERMINAL FLOWER 1transcription in floral meristems on the apex periphery.
TERMINAL FLOWER 1, in turn, can inhibit the activity of meristem identity genes at the centre of the shoot apex in two ways; first by delaying their upregulation, and second, by preventing the meristem from responding to LEAFY or APETALA 1. We suggest that the wild-type pattern of TERMINAL FLOWER 1 and floral meristem identity gene expression depends on the relative timing of their upregulation.
The Drosophila kismet gene is related to chromatin-remodeling factors and is required for both segmentation and segment identity
Authors: Daubresse Gary , Deuring Renate , Moore Lisa , Papoulas Ophelia , Zakrajsek Irena , Waldrip W. Ross , Scott Matthew P. , Kennison James A. , Tamkun John W. 
Published: April 2021

ABSTRACT
The Drosophila kismet gene was identified in a screen for dominant suppressors of Polycomb, a repressor of homeotic genes. Here we show that kismet mutations suppress the Polycomb mutant phenotype by blocking the ectopic transcription of homeotic genes. Loss of zygotic kismet function causes homeotic transformations similar to those associated with loss-of-function mutations in the homeotic genes Sex combs reduced and Abdominal-B. kismet is also required for proper larval body segmentation. Loss of maternal kismet function causes segmentation defects similar to those caused by mutations in the pair-rule gene even-skipped. The kismet gene encodes several large nuclear proteins that are ubiquitously expressed along the anterior-posterior axis. The Kismet proteins contain a domain conserved in the trithorax group protein Brahma and related chromatin-remodeling factors, providing further evidence that alterations in chromatin structure are required to maintain the spatially restricted patterns of homeotic gene transcription.
Transcriptional repression by theDrosophilaGiant protein:ciselement positioning provides an alternative means of interpreting an effector gradient
Authors: Hewitt Gavin F. , Strunk Bethany S. , Margulies Carla , Priputin Tory , Wang Xi-De , Amey Roxane , Pabst Brandon A. , Kosman Dave , Reinitz John , Arnosti David N. 
Published: April 2021

ABSTRACTEarly developmental patterning of the Drosophila embryo is driven by the activities of a diverse set of maternally and zygotically derived transcription factors, including repressors encoded by gap genes such as Krüppel, knirps, giant and the mesoderm-specific snail. The mechanism of repression by gap transcription factors is not well understood at a molecular level. Initial characterization of these transcription factors suggests that they act as short-range repressors, interfering with the activity of enhancer or promoter elements 50 to 100 bp away. To better understand the molecular mechanism of short-range repression, we have investigated the properties of the Giant gap protein. We tested the ability of endogenous Giant to repress when bound close to the transcriptional initiation site and found that Giant effectively represses a heterologous promoter when binding sites are located at −55 bp with respect to the start of transcription. Consistent with its role as a short-range repressor, as the binding sites are moved to more distal locations, repression is diminished. Rather than exhibiting a sharp ‘step-function’ drop-off in activity, however, repression is progressively restricted to areas of highest Giant concentration. Less than a two-fold difference in Giant protein concentration is sufficient to determine a change in transcriptional status of a target gene. This effect demonstrates that Giant protein gradients can be differentially interpreted by target promoters, depending on the exact location of the Giant binding sites within the gene. Thus, in addition to binding site affinity and number, cis element positioning within a promoter can affect the response of a gene to a repressor gradient. We also demonstrate that a chimeric Gal4-Giant protein lacking the basic/zipper domain can specifically repress reporter genes, suggesting that the Giant effector domain is an autonomous repression domain.
Cis-regulatory elements of the mitotic regulator, string/Cdc25
Authors: Lehman Dara A. , Patterson Briony , Johnston Laura A. , Balzer Tracy , Britton Jessica S. , Saint Robert , Edgar Bruce A. 
Published: April 2021

Abstract
Mitosis in most Drosophila cells is triggered by brief bursts of transcription of string (stg), a Cdc25-type phosphatase that activates the mitotic kinase, Cdk1 (Cdc2). To understand how string transcription is regulated, we analyzed the expression of string-lacZ reporter genes covering ∼40 kb of the string locus. We also tested protein coding fragments of the string locus of 6 kb to 31.6 kb for their ability to complement loss of string function in embryos and imaginal discs. A plethora of cis-acting elements spread over &gt;30 kb control string transcription in different cells and tissue types. Regulatory elements specific to subsets of epidermal cells, mesoderm, trachea and nurse cells were identified, but the majority of the string locus appears to be devoted to controlling cell proliferation during neurogenesis. Consistent with this, compact promotor-proximal sequences are sufficient for string function during imaginal disc growth, but additional distal elements are required for the development of neural structures in the eye, wing, leg and notum. We suggest that, during evolution, cell-type-specific control elements were acquired by a simple growth-regulated promoter as a means of coordinating cell division with developmental processes, particularly neurogenesis.
her4, a zebrafish homologue of the Drosophila neurogenic gene E(spl), is a target of NOTCH signalling
Authors: Takke Christina , Dornseifer Peter , Weizsäcker Elisabeth v. , Campos-Ortega José A. 
Published: April 2021

Abstract
her4 encodes a zebrafish bHLH protein of the HAIRY-E(SPL) family. The gene is transcribed in a complex pattern in the developing nervous system and in the hypoblast. During early neurogenesis, her4 expression domains include the regions of the neural plate from which primary neurons arise, suggesting that the gene is involved in directing their development. Indeed, misexpression of specific her4 variants leads to a reduction in the number of primary neurons formed. The amino-terminal region of HER4, including the basic domain, and the region between the putative helix IV and the carboxy-terminal tetrapeptide WRPW are essential for this effect, since HER4 variants lacking either of these regions are non-functional. However, the carboxy-terminal WRPW itself is dispensable. We have examined the interrelationships between deltaD, deltaA, notch1, her4 and neurogenin1 by means of RNA injections. her4 is involved in a regulatory feedback loop which modulates the activity of the proneural gene neurogenin, and as a consequence, of deltaA and deltaD. Activation of notch1 leads to strong activation of her4, to suppression of neurogenin transcription and, ultimately, to a reduction in the number of primary neurons. These results suggest that her4 acts as a target of notch-mediated signals that regulate primary neurogenesis.
Cell cycle-dependent sequencing of cell fate decisions in Caenorhabditis elegans vulva precursor cells
Authors: Ambros Victor 
Published: April 2021

Abstract
In Caenorhabditis elegans, the fates of the six multipotent vulva precursor cells (VPCs) are specified by extracellular signals. One VPC expresses the primary (1°) fate in response to a Ras-mediated inductive signal from the gonad. The two VPCs flanking the 1° cell each express secondary (2°) fates in response to lin-12-mediated lateral signaling. The remaining three VPCs each adopt the non-vulval tertiary (3°) fate. Here I describe experiments examining how the selection of these vulval fates is affected by cell cycle arrest and cell cycle-restricted lin-12 activity. The results suggest that lin-12 participates in two developmental decisions separable by cell cycle phase: lin-12 must act prior to the end of VPC S phase to influence a 1° versus 2° cell fate choice, but must act after VPC S phase to influence a 3° versus 2° cell fate choice. Coupling developmental decisions to cell cycle transitions may provide a mechanism for prioritizing or ordering choices of cell fates for multipotential cells.