bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear β-catenin and the development of bilateral symmetry in normal and LiCl-exposed chick embryos
Authors: Roeser Tobias , Stein Stefan , Kessel Michael 
Published: April 2021

ABSTRACT
Studies in Xenopus laevis and zebrafish suggest a key role for β-catenin in the specification of the axis of bilateral symmetry. In these organisms, nuclear β-catenin demarcates the dorsalizing centers. We have asked whether β-catenin plays a comparable role in the chick embryo and how it is adapted to the particular developmental constraints of chick development. The first nuclear localization of β-catenin is observed in late intrauterine stages of development in the periphery of the blastoderm, the developing area opaca and marginal zone. Obviously, this early, radially symmetric domain does not predict the future organizing center of the embryo. During further development, cells containing nuclear β-catenin spread under the epiblast and form the secondary hypoblast. The onset of hypoblast formation thus demarcates the first bilateral symmetry in nuclear β-catenin distribution. Lithium chloride exposure also causes ectopic nuclear localization of β-catenin in cells of the epiblast in the area pellucida. Embryos treated before primitive streak formation become completely radialized, as shown by the expression of molecular markers, CMIX and GSC. Lithium treatments performed during early or medium streak stages cause excessive development of the anterior primitive streak, node and notochord, and lead to a degeneration of prospective ventral and posterior structures, as shown by the expression of the molecular markers GSC, CNOT1, BMP2 and Ch-Tbx6L. In summary, we found that in spite of remarkable spatiotemporal differences, β-catenin acts in the chick in a manner similar to that in fish and amphibia.
Composite signalling from Serrate and Delta establishes leg segments in Drosophila through Notch
Authors: Bishop S. A. , Klein T. , Arias A. Martinez , Couso J. P. 
Published: April 2021

ABSTRACT
The receptor protein NOTCH and its ligands SERRATE and DELTA are involved in many developmental processes in invertebrates and vertebrates alike. Here we show that the expression of the Serrate and Delta genes patterns the segments of the leg in Drosophila by a combination of their signalling activities. Coincident stripes of Serrate and Delta expressing cells activate Enhancer of split expression in adjacent cells through Notch signalling. These cells form a patterning boundary from which a putative secondary signal leads to the development of leg joints. Elsewhere in the tarsal segments, signalling by DELTA and NOTCH is necessary for the development of non-joint parts of the leg. We propose that these two effects result from different thresholds of NOTCH activation, which are translated into different downstream gene expression effects. We propose a general mechanism for creation of boundaries by Notch signalling.
A short region of its homeodomain is necessary for Engrailed nuclear export and secretion
Authors: Maizel Alexis , Bensaude Olivier , Prochiantz Alain , Joliot Alain 
Published: April 2021

ABSTRACTEngrailed homeoprotein, a transcription factor involved in midbrain/hindbrain patterning, primarily localizes to the cell nucleus. However, significant amounts of the protein are also found in the cell cytoplasm or associated with membrane microdomains enriched in cholesterol and glycosphingoglycolipids (Joliot, A., Trembleau, A., Raposo, G., Calvet, S., Volovitch, M. and Prochiantz, A. (1997) Development 124, 1865-1875). This non-nuclear localization, observed in vitro and in vivo, led us to investigate the possibility that Engrailed be transferred between nuclear and non-nuclear compartments. Monkey COS-7 cells expressing chick Engrailed-2 (cEN2) were fused with 3T3 mouse fibroblasts and the passage of cEN2 from COS-7 to 3T3 nuclei was followed in the interspecies heterokaryons. We find that, 10 minutes following cell fusion, cEN2 is detected in the 3T3 nuclei of 80% of the heterokaryons demonstrating rapid cEN2 nuclear export. Export from donor nuclei can be saturated and is strongly reduced after deletion of a 11 amino acid-long Δ1 sequence present within a slightly larger domain that extends between helices 2 and 3 of the homeodomain and shows strong similarities with leucine-rich nuclear export signals (NES). This putative NES, when fused with a nuclear reporter protein, allows its nuclear export, demonstrating that it is not only necessary but also sufficient for nuclear export and can therefore be considered as a true nuclear export sequence. In an earlier report (Joliot, A., Maizel, A., Rosenberg, D., Trembleau, A., Dupas, S., Volovitch, M. and Prochiantz, A. (1998) Current Biology 8, 856-863), we demonstrated that the Δ1 sequence is necessary for the access of cEN2 to the lumen of a membrane compartment and for its intercellular transfer. The present study thus strongly suggests that the regulation of Engrailed nuclear export could play a role not only in Engrailed transcriptional activity but also in its ability to gain access to a secretory compartment.
Starvation promotes Dictyostelium development by relieving PufA inhibition of PKA translation through the YakA kinase pathway
Authors: Souza Glaucia Mendes , Silva Aline Maria da , Kuspa Adam 
Published: April 2021

ABSTRACT
When nutrients are depleted, Dictyostelium cells undergo cell cycle arrest and initiate a developmental program that ensures survival. The YakA protein kinase governs this transition by regulating the cell cycle, repressing growth-phase genes and inducing developmental genes. YakA mutants have a shortened cell cycle and do not initiate development. A suppressor of yakA that reverses most of the developmental defects of yakA− cells, but none of their growth defects was identified. The inactivated gene, pufA, encodes a member of the Puf protein family of translational regulators. Upon starvation, pufA− cells develop precociously and overexpress developmentally important proteins, including the catalytic subunit of cAMP-dependent protein kinase, PKA-C. Gel mobility-shift assays using a 200-base segment of PKA-C’s mRNA as a probe reveals a complex with wild-type cell extracts, but not with pufA− cell extracts, suggesting the presence of a potential PufA recognition element in the PKA-C mRNA. PKA-C protein levels are low at the times of development when this complex is detectable, whereas when the complex is undetectable PKA-C levels are high. There is also an inverse relationship between PufA and PKA-C protein levels at all times of development in every mutant tested. Furthermore, expression of the putative PufA recognition elements in wild-type cells causes precocious aggregation and PKA-C overexpression, phenocopying a pufA mutation. Finally, YakA function is required for the decline of PufA protein and mRNA levels in the first 4 hours of development. We propose that PufA is a translational regulator that directly controls PKA-C synthesis and that YakA regulates the initiation of development by inhibiting the expression of PufA. Our work also suggests that Puf protein translational regulation evolved prior to the radiation of metazoan species.
P element homing to the Drosophila bithorax complex
Authors: Bender Welcome , Hudson Andrew 
Published: April 2021

ABSTRACT
P elements containing a 7 kb DNA fragment from the middle of the Drosophila bithorax complex insert preferentially into the bithorax complex or into the adjacent chromosome regions. This ‘homing’ property is similar to that reported for the engrailed promoter (Hama, C., Ali, Z. and Kornberg, T. B. (1990) Genes Dev. 4, 1079-1093). The 7 kb fragment does not contain any known promoter, but it acts as a boundary element separating adjacent segmental domains. An enhancer-trap P element was constructed with the homing fragment and the selectable marker flanked by FRT sites. P insertions can be trimmed down by Flp-mediated recombination to just the lacZ reporter, so that the β-galactosidase pattern is not influenced by sequences inside the P element. Twenty insertions into the bithorax complex express β-galactosidase in segmentally limited patterns, reflecting the segmental domains of the bithorax complex where the elements reside. The mapping of segmental domains has now been revised, with enlargement of the abx/bx, bxd/pbx, and the iab-3 domains. The FRT sites in the P elements permit recombination between pairs of elements on opposite chromosomes, to generate duplications or deletions of the DNA between the two insertion sites. Using this technique, the length of the Ultrabithorax transcription unit was varied from 37 to 138 kb, but there was surprisingly little effect on Ultrabithorax function.
Suppressor of Fused opposes Hedgehog signal transduction by impeding nuclear accumulation of the activator form of Cubitus interruptus
Authors: Méthot Nathalie , Basler Konrad 
Published: April 2021

ABSTRACT
Hedgehog controls the expression of key developmental genes through the conversion of the transcription factor Cubitus interruptus (Ci) into either an activator (Ci[act]) or a repressor (Ci[rep]) form. Proteolytic cleavage of full-length Ci is important for the generation of Ci[rep], but little is known about how Ci[act] arises in response to Hh. Here we examine Hh signal transduction components for their role in the conversion of full-length Ci into either Ci[act] or Ci[rep]. We report that Cos2, PKA and Fused are necessary for the generation of Ci[rep], whereas the inhibition of either Cos2 or PKA activity is a prerequisite for Ci[act] formation. Fused (Fu) kinase stimulates a constitutively active form of Ci in a Hh-dependent manner, suggesting that Fu enhances the activity rather than the formation of Ci[act]. Su(fu) reduces the nuclear accumulation of the constitutively active form of Ci, arguing that Su(fu) can function subsequent to Ci[act] formation. We propose that Hh induces target gene expression by a two-step mechanism in which Ci[act] is first formed and then accumulates in the nucleus via Fu-induced neutralization of Su(fu) activity.
Placental vascularisation requires the AP-1 component Fra1
Authors: Schreiber Martin , Wang Zhao-Qi , Jochum Wolfram , Fetka Ingrid , Elliott Candace , Wagner Erwin F. 
Published: April 2021

ABSTRACTFra1 is an immediate-early gene encoding a member of the AP-1 transcription factor family, which has diverse roles in development and oncogenesis. To determine the function of Fra1 in mouse development, the gene was inactivated by gene targeting. Foetuses lacking Fra1 were severely growth retarded and died between E10.0 and E10.5, owing to defects in extra-embryonic tissues. The placental labyrinth layer, where X-gal staining revealed expression of Fra1, was reduced in size and largely avascular, owing to a marked decrease in the number of vascular endothelial cells, as shown by the lack of Flk1 expression. In contrast, the spongiotrophoblast layer was unaffected and expressed the marker genes 4311 (Tpbp) and Flt1. Furthermore, mutant foetuses exhibited yolk-sac defects that may contribute to their growth retardation and lethality. Importantly, when the placental defect was rescued by injection of Fra1−/−ES cells into tetraploid wild-type blastocysts, Fra1−/−pups were obtained that were no longer growth retarded and survived up to 2 days after birth without apparent phenotypic defects. These data indicate that a defect in the extra-embryonic compartment is causal to the observed lethality, and suggest that Fra1 plays a crucial role in establishing normal vascularisation of the placenta.
Activation tagging of theLEAFY PETIOLEgene affects leaf petiole development inArabidopsis thaliana
Authors: Graaff Eric van der , Dulk-Ras Amke Den , Hooykaas Paul J. J. , Keller Beat 
Published: April 2021

ABSTRACTIn a screen for leaf developmental mutants we have isolated an activator T-DNA-tagged mutant that produces leaves without a petiole. In addition to that leafy petiole phenotype this lettuce (let) mutant shows aberrant inflorescence branching and silique shape. The LEAFY PETIOLE (LEP) gene is located close to the right border of the T-DNA insert linked with these dominant phenotypes and encodes a protein with a domain with similarity to the DNA binding domain of members of the AP2/EREBP family of transcription factors. Introduction of the activation-tagged LEP gene in wild-type plants conferred all the phenotypic aberrations mentioned above. The leafy petiole phenotype consists of a conversion of the proximal part of the leaf from petiole into leaf blade, which means that leaf development in let is disturbed along the proximodistal axis. Therefore, LEP is involved in either cell division activity in the marginal meristem or patterning along the proximodistal axis.
Apterous mediates development of direct flight muscles autonomously and indirect flight muscles through epidermal cues
Authors: Ghazi Arjuman , Anant Sumita , VijayRaghavan K. 
Published: April 2021

ABSTRACT
Two physiologically distinct types of muscles, the direct and indirect flight muscles, develop from myoblasts associated with the Drosophila wing disc. We show that the direct flight muscles are specified by the expression of Apterous, a Lim homeodomain protein, in groups of myoblasts. This suggests a mechanism of cell-fate specification by labelling groups of fusion competent myoblasts, in contrast to mechanisms in the embryo, where muscle cell fate is specified by single founder myoblasts. In addition, Apterous is expressed in the developing adult epidermal muscle attachment sites. Here, it functions to regulate the expression of stripe, a gene that is an important element of early patterning of muscle fibres, from the epidermis. Our results, which may have broad implications, suggest novel mechanisms of muscle patterning in the adult, in contrast to embryonic myogenesis.
Ectopic Hoxa2 induction after neural crest migration results in homeosis of jaw elements in Xenopus
Authors: Pasqualetti Massimo , Ori Michela , Nardi Irma , Rijli Filippo M. 
Published: April 2021

ABSTRACT
Hox genes are required to pattern neural crest (NC) derived craniofacial and visceral skeletal structures. However, the temporal requirement of Hox patterning activity is not known. Here, we use an inducible system to establish Hoxa2 activity at distinct NC migratory stages in Xenopus embryos. We uncover stage-specific effects of Hoxa2 gain-of-function suggesting a multistep patterning process for hindbrain NC. Most interestingly, we show that Hoxa2 induction at postmigratory stages results in mirror image homeotic transformation of a subset of jaw elements, normally devoid of Hox expression, towards hyoid morphology. This is the reverse phenotype to that observed in the Hoxa2 knockout. These data demonstrate that the skeletal pattern of rhombomeric mandibular crest is not committed before migration and further implicate Hoxa2 as a true selector of hyoid fate. Moreover, the demonstration that the expression of Hoxa2 alone is sufficient to transform the upper jaw and its joint selectively may have implications for the evolution of jaws.
Papilin in development; a pericellular protein with a homology to the ADAMTS metalloproteinases
Authors: Kramerova Irina A. , Kawaguchi Nobuko , Fessler Liselotte I. , Nelson Robert E. , Chen Yali , Kramerov Andrei A. , Kusche-Gullberg Marion , Kramer James M. , Ackley Brian D. , Sieron Aleksander L. , Prockop Darwin J. , Fessler John H. 
Published: April 2021

ABSTRACT
Papilin is an extracellular matrix glycoprotein that we have found to be involved in, (1) thin matrix layers during gastrulation, (2) matrix associated with wandering, phagocytic hemocytes, (3) basement membranes and (4) space-filling matrix during Drosophila development. Determination of its cDNA sequence led to the identification of Caenorhabditis and mammalian papilins. A distinctly conserved ‘papilin cassette’ of domains at the amino-end of papilins is also the carboxyl-end of the ADAMTS subgroup of secreted, matrix-associated metalloproteinases; this cassette contains one thrombospondin type 1 (TSR) domain, a specific cysteine-rich domain and several partial TSR domains. In vitro, papilin non-competitively inhibits procollagen N-proteinase, an ADAMTS metalloproteinase. Inhibiting papilin synthesis in Drosophila or Caenorhabditis causes defective cell arrangements and embryonic death. Ectopic expression of papilin in Drosophila causes lethal abnormalities in muscle, Malpighian tubule and trachea formation. We suggest that papilin influences cell rearrangements and may modulate metalloproteinases during organogenesis.
Adult corneal epithelium basal cells possess the capacity to activate epidermal, pilosebaceous and sweat gland genetic programs in response to embryonic dermal stimuli
Authors: Ferraris Corinne , Chevalier Genevieve , Favier Bertrand , Jahoda Colin A. B. , Dhouailly Danielle 
Published: April 2021

ABSTRACT
Recent work has shown remarkable plasticity between neural and hematopoeitic, as well as between hematopoeitic and muscle stem cells, depending on environmental stimuli (Fuchs, E. and Segre, J. A. (2000) Cell 100, 143-155). Stem cells give rise to a proliferative transient amplifying population (TA), which is generally considered to be irreversibly committed. Corneal epithelium provides a particularly useful system for studying the ability of TA cells to activate different genetic programs in response to a change in their fibroblast environment. Indeed, corneal stem and TA cells occupy different localities – stem cells at the periphery, and TA cells more central (Lehrer, M. S., Sun, T. T. and Lavker, R. M. (1998) J. Cell Sci. 111, 2867-2875) – and thus can be discretely dissected from each other. It is well known that pluristratified epithelia of cornea and skin display distinct programs of differentiation: corneal keratinocytes express keratin pair K3/K12 and epidermal keratinocytes keratin pair K1-2/K10; moreover, the epidermis forms cutaneous appendages, which express their own set of keratins. In our experiments, central adult rabbit corneal epithelium was thus associated either with a mouse embryonic dorsal, upper-lip or plantar dermis before grafting onto nude mice. Complementary experiments were performed using adult mouse corneal epithelium from the Rosa 26 strain. The origin of the differentiated structures were identified in the first case by Hoechst staining and in the second by the detection of β-galactosidase activity. The results show that adult central corneal cells are able to respond to specific information originating from embryonic dermis. They give rise first to a new basal stratum, which does not express anymore corneal-type keratins, then to pilosebaceous units, or sweat glands, depending of the dermis, and finally to upper layers expressing epidermal-type keratins. Our results provide the first evidence that a distinct TA cell population can be reprogrammed.
Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of β-cell formation in the pancreas
Authors: Sander Maike , Sussel Lori , Conners Jennifer , Scheel David , Kalamaras Julie , Cruz Filemon Dela , Schwitzgebel Valerie , Hayes-Jordan Andrea , German Michael 
Published: April 2021

ABSTRACT
Most insulin-producing β-cells in the fetal mouse pancreas arise during the secondary transition, a wave of differentiation starting at embryonic day 13. Here, we show that disruption of homeobox gene Nkx6.1 in mice leads to loss of β-cell precursors and blocks β-cell neogenesis specifically during the secondary transition. In contrast, islet development in Nkx6.1/Nkx2.2 double mutant embryos is identical to Nkx2.2 single mutant islet development: β-cell precursors survive but fail to differentiate into β-cells throughout development. Together, these experiments reveal two independently controlled pathways for β-cell differentiation, and place Nkx6.1 downstream of Nkx2.2 in the major pathway of β-cell differentiation.
Indian Hedgehog coordinates endochondral bone growth and morphogenesis via Parathyroid Hormone related-Protein-dependent and -independent pathways
Authors: Karp Seth J. , Schipani Ernestina , St-Jacques* Benoit , Hunzelman Joy , Kronenberg Henry , McMahon Andrew P. 
Published: April 2021

ABSTRACT
Indian hedgehog (Ihh) and Parathyroid Hormone-related Protein (PTHrP) play a critical role in the morphogenesis of the vertebrate skeleton. Targeted deletion of Ihh results in short-limbed dwarfism, with decreased chondrocyte proliferation and extensive hypertrophy, features shared by mutants in PTHrP and its receptor. Activation of Ihh signaling upregulates PTHrP at the articular surface and prevents chondrocyte hypertrophy in wild-type but not PTHrP null explants, suggesting that Ihh acts through PTHrP. To investigate the relationship between these factors during development of the appendicular skeleton, mice were produced with various combinations of an Ihh null mutation (Ihh–/–), a PTHrP null mutation (PTHrP–/–), and a constitutively active PTHrP/Parathyroid hormone Receptor expressed under the control of the Collagen II promoter (PTHrPR*). PTHrPR* rescues PTHrP–/– embryos, demonstrating this construct can completely compensate for PTHrP signalling. At 18.5 dpc, limb skeletons of Ihh, PTHrP compound mutants were identical to Ihh single mutants suggesting Ihh is necessary for PTHrP function. Expression of PTHrPR* in chondrocytes of Ihh–/– mice prevented premature chondrocyte hypertrophy but did not rescue either the short-limbed dwarfism or decreased chondrocyte proliferation. These experiments demonstrate that the molecular mechanism that prevents chondrocyte hypertrophy is distinct from that which drives proliferation. Ihh positively regulates PTHrP, which is sufficient to prevent chondrocyte hypertrophy and maintain a normal domain of cells competent to undergo proliferation. In contrast, Ihh is necessary for normal chondrocyte proliferation in a pathway that can not be rescued by PTHrP signaling. This identifies Ihh as a coordinator of skeletal growth and morphogenesis, and refines the role of PTHrP in mediating a subset of Ihh’s actions.
Sloppy paired acts as the downstream target of Wingless in the Drosophila CNS and interaction between sloppy paired and gooseberry inhibits sloppy paired during neurogenesis
Authors: Bhat Krishna Moorthi , Beers Erik H. van , Bhat Prema 
Published: April 2021

ABSTRACT
Wingless (Wg) and other Wnt proteins play a crucial role in a number of developmental decisions in a variety of organisms. In the ventral nerve cord of the Drosophila embryo, Wg is non-autonomously required for the formation and specification of a neuronal precursor cell, NB4-2. NB4-2 gives rise to a well-studied neuronal lineage, the RP2/sib lineage. While the various components of the Wg-signaling pathway are also required for generating NB4-2, the target gene(s) of this pathway in the signal-receiving cell is not known. In this paper, we show that sloppy paired 1 and sloppy paired 2 function as the downstream targets of the Wg signaling to generate the NB4-2 cell. Thus, while the loss-of-function mutations in wg and slp have the same NB4-2 formation and specification defects, these defects in wg mutants can be rescued by expressing slp genes from a heterologous promoter. That slp genes function downstream of the Wg signaling is also indicated by the result that expression of slp genes is lost from the neuroectoderm in wg mutants and that ectopic expression of wg induces ectopic expression of slp. Finally, previous results show that Gooseberry (Gsb) prevents Wg from specifying NB4-2 identity to the wg-expressing NB5-3. In this paper, we also show that gsb interacts with slp and prevents Slp from specifying NB4-2 identity. Overexpression of slp overcomes this antagonistic interaction and respecifies NB5-3 as NB4-2. This respecification, however, can be suppressed by a simultaneous overexpression of gsb at high levels. This mechanism appears to be responsible for specifying NB5-3 identity to a row 5 neuroblast and preventing Wg from specifying NB4-2 identity to that cell.