bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Caenorhabditis elegans NK-2 class homeoprotein CEH-22 is involved in combinatorial activation of gene expression in pharyngeal muscle
Authors: Okkema Peter G. , Fire Andrew 
Published: April 2021

ABSTRACT
The pharyngeal muscles of Caenorhabditis elegans are single sarcomere muscles used for feeding. Like vertebrate cardiac and smooth muscles, C. elegans pharyngeal muscle does not express any of the known members of the MyoD family of myogenic factors. To identify mechanisms regulating gene expression in this tissue, we have characterized a pharyngeal muscle-specific enhancer from myo-2, a myosin heavy chain gene expressed exclusively in pharyngeal muscle. Assaying enhancer function in transgenic animals, we identified three subelements, designated A, B and C, that contribute to myo-2 enhancer activity. These subelements are individually inactive; however, any combination of two or more subelements forms a functional enhancer. The B and C subelements have distinct cell type specificities. A duplication of B activates transcription in a subset of pharyngeal muscles (m3, m4, m5 and m7). A duplication of C activates transcription in all pharyngeal cells, muscle and non-muscle. Thus, the activity of the myo-2 enhancer is regulated by a combination of pharyngeal muscle-type-specific and organ-specific signals. Screening a cDNA expression library, we identified a gene encoding an NK-2 class homeodomain protein, CEH-22, that specifically binds a site necessary for activity of the B subelement. CEH-22 protein is first expressed prior to myogenic differentiation and is present in the same subset of pharyngeal muscles in which B is active. Expression continues throughout embryonic and larval development. This expression pattern suggests CEH-22 plays a key role in pharyngeal muscle-specific activity of the myo-2 enhancer.
Wnt-1-dependent regulation of local E-cadherin and αN-catenin expression in the embryonic mouse brain
Authors: Shimamura Kenji , Hirano Shinji , McMahon Andrew P. , Takeichi Masatoshi 
Published: April 2021

ABSTRACT
E-cadherin is transiently expressed in local regions of the embryonic mouse brain, which include several patchy areas on the mesencephalon and diencephalon and their roof plate and part of cerebellar rudiments. In the present study, we compared this E-cadherin expression with that of Wnt-1, which occurs in specific zones in the embryonic brain, and found certain spatiotemporal relations between them: Wnt-1 expression tended to run parallel or overlap with peripheries of the E-cadherin-positive areas. For example, in the dorsal midline, Wnt-1 was expressed at the middle of the roof plate, while E-cadherin was absent in the middle zone but detected in two arrays of marginal roof plate cells. Furthermore, αN-catenin, a cadherin-associated protein, was found to occur at the roof plate of the mesencephalon and diencephalon, coinciding with Wnt-1 expression. The expression of these molecules was then studied in two alleles of the Wnt-1 mutation, Wnt-1sw and Wnt-1neo. In mice homozygous for these mutant genes, E-cadherin expression in the roof plate was up-regulated; the middle E-cadherin-negative zone disappeared. Moreover, E-cadherin expression in the roof plate began earlier in the mutant mice than in wild-type mice. On the contrary, αN-catenin expression in the dorsal midline was suppressed in these mutants. These changes in cadherin and catenin expression occurred at the level of mRNA expression. These results suggest that the Wnt-1 signal is, either directly or indirectly, involved in the regulation of expression of E-cadherin and αN-catenin in restricted regions of the embryonic brain. This mechanism may contribute to the patterning of the expression of these adhesion-related proteins in the embryonic brain.
Exposure to retinoic acid before or after the onset of somitogenesis reveals separate effects on rhombomeric segmentation and 3′ HoxB gene expression domains
Authors: Wood Heather , Pall Gurman , Morriss-Kay Gillian 
Published: April 2021

ABSTRACT
We have compared the relationship between the patterns of altered morphogenesis and of altered gene expression in mouse embryos exposed to excess retinoic acid (RA) (a) just before and (b) just after the onset of somitic segmentation (day 7.75 to day 8.25). Exposure to RA prior to the onset of somitic segmentation results in suppression of rhombomeric (but not somitic) segmentation, and conversion of the genetic identity of the whole preotic hindbrain to that of rhombomere 4. In contrast, exposure to RA at early somite stages results in near-normal rhombomeric segmentation; rhombomeric gene expression domains indicate that only rhombomere 2 has changed its genetic identity to that of rhombomere 4, the other preotic segments showing normal expression patterns for HoxB genes and Krox-20. The results indicate that RA has separable effects (1) on the genes mediating the process of rhombomeric segmentation per se, such as Krox-20, and (2) on the genes that influence the nature of the structures that subsequently develop from the individual rhombomeres, such as the Hox genes.
Two maternal genes, apx-1 and pie-1, are required to distinguish the fates of equivalent blastomeres in the early Caenorhabditis elegans embryo
Authors: Mango Susan E. , Thorpe Christopher J. , Martin Paula R. , Chamberlain Stephen H. , Bowerman Bruce 
Published: April 2021

ABSTRACT
In a 4-cell Caenorhabditis elegans embryo, two sister blas- tomeres called ABa and ABp are born with equivalent developmental potential, but eventually produce distinct patterns of cell fate. The different fates of ABa and ABp are specified at least in part by inductive interactions with neighboring blastomeres. Previous studies indicate that, at the 4-cell stage, a signal from the posterior-most blas- tomere, P2, is required for ABp to produce at least one of its unique cell types. This P2/ABp interaction depends on glp-1, a putative receptor for intercellular interactions.
To investigate this early induction further, we isolated mutants in which ABp developed abnormally. We describe the effects of recessive mutations in apx-1, a maternal gene that appears to be required for P2 to signal ABp. In embryos from mothers homozygous for mutations in apx- 1 (apx-1 embryos), ABp fails to produce its characteristic cell types. Instead, ABp from apx-1 embryos develops more like its sister ABa: it produces ABa-like pharyngeal cells and it recapitulates ABa-like cell lineages. Because mutations in apx-1 affect the development of only the ABp blastomere, we suggest that the wild-type gene encodes a component of the P2/ABp signalling pathway. To explain the observation that ABp in apx-1 embryos adopts an ABa- like fate, we propose a model in which the P2 signal is required to break the initial equivalence of ABa and ABp. We performed two independent tests of this model. First, we examined ABp development in pie-1 mutant embryos, in which P2 adopts the identity of another blastomere. We find that, in pie-1 embryos, ABp fails to produce its char- acteristic cell types and instead adopts a fate similar to that of ABa. We conclude that the changed identity of P2 in pie- 1 embryos prevents the P2/ABp interaction. As a second test, we examined ABp development in wild-type embryos after physically removing P2. These operated embryos produce extra pharyngeal cells, consistent with our proposal that a signal from P2 breaks the initially equiva- lent developmental state of ABa and ABp. We discuss the possibility that apx-1 acts as a ligand in this glp-1- dependent signalling pathway.
marbles mutants: uncoupling cell determination and nuclear migration in the developing Drosophila eye
Authors: Fischer-Vize Janice A. , Mosley Kathleen L. 
Published: April 2021

ABSTRACT
Morphogenesis of a multicellular structure requires not only that cells are specified to express particular gene products, but also that cells move to adopt characteristic shapes and positions. Little is known about how these two aspects of morphogenesis are coordinated. The developing Drosophila compound eye is a monolayer, in which cells are suspended between apical and basal membranes and assemble sequentially into hundreds of unit eyes, or facets, guided by a series of cell interactions. As cells are determined to join the facet, their nuclei and cell bodies rise apically and then settle into position in the cell group. The final nuclear positions determine the shape of the individual cells. We have identified a Drosophila gene called marbles which is required for the apical nuclear migrations that accompany cell determination during eye development. In marbles mutant eyes, the sequence of cell specification that leads to the formation of facets occurs almost normally despite the failure of nuclear migration in many cells. The marbles mutant phenotype reveals that during Drosophila eye development cell determination does not require nuclear migration.
sidecar pollen, an Arabidopsis thaliana male gametophytic mutant with aberrant cell divisions during pollen development
Authors: Chen Yun-Chia Sophia , McCormick Sheila 
Published: April 2021

ABSTRACT
During pollen development each product of meiosis undergoes a stereotypical pattern of cell divisions to give rise to a three-celled gametophyte, the pollen grain. First an asymmetric mitosis generates a larger vegetative cell and a smaller generative cell, then the generative cell undergoes a second mitosis to give rise to two sperm cells. It is unknown how this pattern of cell divisions is controlled. We have identified an Arabidopsis gene, SIDECAR POLLEN, which is required for the normal cell division pattern during pollen development. In the genetic background of the NoO ecotype, sidecar pollen heterozygotes have about 45% wild-type pollen, 48% aborted pollen and 7% pollen with an extra cell. Homozygous sidecar pollen plants have about 20% wild-type pollen, 53% aborted pollen and 27% extra-celled pollen. Similar ratios of sidecar pollen phenotypes are seen in the Columbia ecotype but sidecar pollen is a gametophytic lethal in the Landsberg erecta ecotype. Thus this allele of sidecar pollen shows differential gametophytic penetrance and variable expressivity in different genetic backgrounds. The extra cell has the cell identity of a vegetative cell and is produced prior to any asymmetric microspore mitosis. Pollen tetrad analysis directly demonstrates that SIDECAR POLLEN is indeed expressed in male gametophytes. To our knowledge, scp is the first male gametophytic mutation to be described in Arabidopsis.
A Xenopus nodal-related gene that acts in synergy with noggin to induce complete secondary axis and notochord formation
Authors: Lustig K. D. , Kroll K. , Sun E. , Ramos R. , Elmendorf H. , Kirschner M. W. 
Published: April 2021

ABSTRACT
Using a paracrine assay to screen for signaling proteins that could respecify ectodermal tissue, we isolated a Xenopus gene related to the mouse gene nodal, a member of the TGFβ superfamily. The gene is expressed in three regions in the early Xenopus embryo: first in the gastrula organizer, then in two stripes of cells flanking the posterior notochord in late neurulae, and finally in lateral plate mesoderm restricted to the left side of tailbud-stage embryos. Ectopic expression of the gene induces muscle formation in ectodermal explants and partial secondary axes in whole embryos. Together with noggin, another secreted protein also present in the organizer, it induces notochord formation in ectodermal explants and complete secondary axes in whole embryos. These results suggest that the nodal-related gene may act together with noggin to induce axial pattern during gastrulation and also may play a role in left-right asymmetry generation in the post-gastrula embryo.
Nerve dependency of regeneration: the role of Distal-less and FGF signaling in amphibian limb regeneration
Authors: Mullen Lina M. , Bryant Susan V. , Torok Maureen A. , Blumberg Bruce , Gardiner David M. 
Published: April 2021

ABSTRACT
Dlx-3, a homolog of Drosophila Dll, has been isolated from an axolotl blastema cDNA library, and its expression in developing and regenerating limbs characterized. The normal expression pattern, and the changes that occur during experimental treatments, indicate a correlation between Dlx-3 expression and the establishment of the outgrowth-permitting epidermis. Dlx-3 is expressed at high levels in a distal-to-proximal gradient in the epidermis of developing limb buds, and is upregulated in the apical ectodermal cap (AEC) during limb regeneration. Expression is maximal at the late bud stage of regeneration, coincident with the transition from the early phase of nerve dependency to the later phase of nerve independence. Dlx-3 expression in the epidermis is rapidly downregulated by denervation during the nerve-dependent phase and is unaffected by denervation during the nerve-independent phase. We investigated this relationship between nerves and Dlx-3 expression by implanting FGF-2 beads into regenerates that had been denervated at a nerve-dependent stage. Dlx-3 expression was maintained by FGF-2 after denervation, and regeneration progressed to completion. In addition, we detected FGF-2 protein in the AEC and in nerves, and observed that the level of expression in both tissues decreases dramatically in response to denervation. We conclude that both limb development and regeneration require a permissive epidermis, characterized by Dlx-3 and FGF expression, both of which are maintained by FGF through an autocrine loop. The transformation of the limb epidermis into a functional AEC that produces and responds to FGF autocatalytically, is presumed to be induced by FGF. Since nerves appear to be a source of this priming FGF, it is possible that a member of the FGF family of growth factors is the elusive neurotrophic factor of limb regeneration.
RtoA links initial cell type choice to the cell cycle in Dictyostelium
Authors: Wood Salli A. , Ammann Robin R. , Brock Debra A. , Li Lily , Spann Timothy , Gomer Richard H. 
Published: April 2021

ABSTRACT
In Dictyostelium, initial cell type choice is correlated with the cell-cycle phase of the cell at the time of starvation. We have isolated a mutant, ratioA (rtoA), with a defect in this mechanism that results in an abnormally high percentage of prestalk cells. The rtoA gene has been cloned and sequenced and codes for a novel protein. The cell cycle is normal in rtoA. In the wild type, prestalk cells differentiate from those cells in S or early G2 phase at starvation and prespore cells from cells in late G2 or M phase at starvation. In rtoA mutants, both prestalk and prespore cells originate randomly from cells in any phase of the cell cycle at starvation.
Cadherin-mediated cell adhesion and cell motility in Drosophila trachea regulated by the transcription factor Escargot
Authors: Tanaka-Matakatsu Miho , Uemura Tadashi , Oda Hiroki , Takeichi Masatoshi , Hayashi Shigeo 
Published: April 2021

ABSTRACT
Coordination of cell motility and adhesion is essential for concerted movement of tissues during animal morphogenesis. The Drosophila tracheal network is formed by branching, migration and fusion of tubular ectodermal epithelia. Tracheal tip cells, located at the end of each branch that is going to fuse, extend filopodia to search for targets and later change their cell shape to a seamless ring to allow passage of lumen. The cell adhesion molecule DE-cadherin accumulates at the site of contact to form a ring that marks the site of lumen entry and is essential for the fusion. DE-cadherin expression in tip cells of a subset of branches is dependent on escargot, a zinc finger gene expressed in all tip cells. Such escargot mutant tip cells failed to adhere to each other and continued to search for alternative targets by extending long filopodia. We present evidence indicating escargot positively regulates transcription of the DE-cadherin gene, shotgun. Overexpression of DE-cadherin rescued the defect in one of the fusion points in escargot mutants, demonstrating an essential role of DE-cadherin in target recognition and identifying escargot as a key regulator of cell adhesion and motility in tracheal morphogenesis.
Targeted disruption of the Hoxb-2 locus in mice interferes with expression of Hoxb-1 and Hoxb-4
Authors: Barrow Jeffery R. , Capecchi Mario R. 
Published: April 2021

ABSTRACT
Mice with a disruption in the hoxb-2 locus were generated by gene targeting. 75% of the hoxb-2 mutant homozygotes died within 24 hours of birth. While a majority of these mice had severe sternal defects that compromised their ability to breathe, some had relatively normal sternum morphology, suggesting that one or more additional factor(s) contributed to neonatal lethality. At 3-3.5 weeks of age, half of the remaining hoxb-2 homozygotes became weak and subsequently died. All of the mutants that survived to 3 weeks of age showed marked facial paralysis similar to, but more severe than, that reported for hoxb-1 mutant homozygotes (Goddard, J. M., Rossel, M., Manley, N. R. and Capecchi, M. R. (1996) Development 122, 3217-3228). As for the hoxb-1 mutations, the facial paralysis observed in mice homozygous for the hoxb-2 mutation results from a failure to form the somatic motor component of the VIIth (facial) nerve which controls the muscles of facial expression. Features of this phenotype closely resemble the clinical signs associated with Bell’s Palsy and Moebius Syndrome in humans. The sternal defects seen in hoxb-2 mutant mice are similar to those previously reported for hoxb-4 mutant mice (Ramirez-Solis, R., Zheng, H., Whiting, J., Krumlauf, R. and Bradley. A. (1993) Cell 73, 279-294). The above results suggest that the hoxb-2 mutant phenotype may result in part from effects of the hoxb-2 mutation on the expression of both hoxb-1 and hoxb-4. Consistent with this proposal, we found that the hoxb-2 mutation disrupts the expression of hoxb-1 in cis. In addition, the hoxb-2 mutation changes the expression of hoxb-4 and the hoxb-4 mutation, in turn, alters the pattern of hoxb-2 expression. Hoxb-2 and hoxb-4 appear to function together to mediate proper closure of the ventral thoracic body wall. Failure in this closure results in severe defects of the sternum.
Hikaru genki protein is secreted into synaptic clefts from an early stage of synapse formation in Drosophila
Authors: Hoshino Mikio , Suzuki Emiko , Nabeshima Yo-ichi , Hama Chihiro 
Published: April 2021

ABSTRACT
The development of neural circuits is regulated by a large number of factors that are localized at distinct neural sites. We report here the localization of one of these factors, hikaru genki (hig) protein, at synaptic clefts in the pupal and adult nervous systems of Drosophila. In hig mutants, unusually frequent bursting activity of the muscles and abnormal motor behavior during the adult stage suggest the misfunction of neuromuscular circuitry. Our immunohistochemical analyses revealed that hig protein, produced by neurons, is secreted from the presynaptic terminals into the spaces between the presynaptic and postsynaptic terminals. In addition, we have found that the localization of this protein in the synaptic spaces temporally correlates with its functional requirement during a critical period that occurs in the middle stage of pupal formation, a period when a number of dendrite and axon growth cones meet to form synapses. These findings indicate that hig protein functions in the formation of functional neural circuits from the early stages of synapse formation.
Two Pax-binding sites are required for early embryonic brain expression of an Engrailed-2 transgene
Authors: Song Dong-Li , Chalepakis Georges , Gruss Peter , Joyner Alexandra L. 
Published: April 2021

ABSTRACT
The temporally and spatially restricted expression of the mouse Engrailed (En) genes is essential for development of the midbrain and cerebellum. The regulation of En-2 expression was studied using in vitro protein-DNA binding assays and in vivo expression analysis in transgenic mice to gain insight into the genetic events that lead to regionalization of the developing brain. A minimum En-2 1.0 kb enhancer fragment was defined and found to contain multiple positive and negative regulatory elements that function in concert to establish the early embryonic midhindbrain expression. Furthermore, the mid-hindbrain regulatory sequences were shown to be structurally and functionally conserved in humans.
The mouse paired-box-containing genes Pax-2, Pax-5 and Pax-8 show overlapping expression with the En genes in the developing brain. Significantly, two DNA-binding sites for Pax-2, Pax-5 and Pax-8 proteins were identified in the 1.0 kb En-2 regulatory sequences, and mutation of the binding sites disrupted initiation and maintenance of expression in transgenic mice. These results present strong molecular evidence that the Pax genes are direct upstream regulators of En-2 in the genetic cascade controlling midhindbrain development. These mouse studies, taken together with others in Drosophila and zebrafish on the role of Pax genes in controlling expression of En family members, indicate that a Pax-En genetic pathway has been conserved during evolution.
Mouse preimplantation blastocysts adhere to cells expressing the transmembrane form of heparin-binding EGF-like growth factor
Authors: Raab Gerhard , Kover Karen , Paria Bibhash C. , Dey Sudhansu K. , Ezzell Robert M. , Klagsbrun Michael 
Published: April 2021

ABSTRACT
Previous studies have shown that heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) mRNA is synthesized in the mouse uterine luminal epithelium, temporally, just prior to implantation, and spatially, only at the site of blastocyst apposition (Das, S. K., Wang, X. N., Paria, B. C., Damm, D., Abraham, J. A., Klagsbrun, M., Andrews, G. K. and Dey, S. K. (1994) Development 120, 1071–1083). HB-EGF is synthesized as a transmembrane protein (HB-EGFTM) that can be processed to release the soluble growth factor. An antibody that cross-reacts only with the transmembrane form detected HB-EGFTM in uterine luminal epithelium in a spatial manner similar to that of HB-EGF mRNA. HB-EGFTM is a juxtacrine growth factor that mediates cell-cell contact. To ascertain if HB-EGFTM could be an adhesion factor for blastocysts, a mouse cell line synthesizing human HB-EGFTM was co-cultured with mouse blastocysts. Cells synthesizing HB-EGFTM adhered to day-4 mouse blasto-cysts more extensively than parental cells or cells synthesizing a constituitively secreted form of HB-EGF. Adhesion of cells synthesizing HB-EGFTM to blastocysts was inhibited by excess recombinant HB-EGF but less so by TGF-α. Adhesion was also inhibited by the synthetic peptide P21 corresponding to the HB-EGF heparin binding domain, and by incubating the blastocysts with heparinase. In addition, adhesion to delayed implanting dormant blastocysts, which lack EGF receptor (EGFR), was diminished relative to normal blastocysts. These results suggested that adhesion between blastocysts and cells synthesizing HB-EGFTM was mediated via interactions with both blastocyst EGFR and heparan sulfate proteoglycan (HSPG). It was concluded that HB-EGFTM, which is synthesized exclusively in the luminal epithelium at the site of blastocyst apposition, and which is a juxtacrine adhesion factor for blastocysts, could be one of the mediators of blastocyst adhesion to the uterus in the process of implantation.