bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emx1 and Emx2 functions in development of dorsal telencephalon
Authors: Yoshida Michio , Suda Yoko , Matsuo Isao , Miyamoto Norimasa , Takeda Naoki , Kuratani Shigeru , Aizawa Shinichi 
Published: April 2021

ABSTRACT
The genes Emx1 and Emx2 are mouse cognates of a Drosophila head gap gene, empty spiracles, and their expression patterns have suggested their involvement in regional patterning of the forebrain. To define their functions we introduced mutations into these loci. The newborn Emx2 mutants displayed defects in archipallium structures that are believed to play essential roles in learning, memory and behavior: the dentate gyrus was missing, and the hippocampus and medial limbic cortex were greatly reduced in size. In contrast, defects were subtle in adult Emx1 mutant brain. In the early developing Emx2 mutant forebrain, the evagination of cerebral hemispheres was reduced and the roof between the hemispheres was expanded, suggesting the lateral shift of its boundary. Defects were not apparent, however, in the region where Emx1 expression overlaps that of Emx2, nor was any defect found in the early embryonic forebrain caused by mutation of the Emx1 gene, of which expression principally occurs within the Emx2-positive region. Emx2 most likely delineates the palliochoroidal boundary in the absence of Emx1 expression during early dorsal forebrain patterning. In the more lateral region of telencephalon, Emx2-deficiency may be compensated for by Emx1 and vice versa. Phenotypes of newborn brains also suggest that these genes function in neurogenesis corresponding to their later expressions.
Specific and redundant functions of Gli2 and Gli3 zinc finger genes in skeletal patterning and development
Authors: Mo Rong , Freer Anne Marie , Zinyk Dawn L. , Crackower Michael A. , Michaud Jacques , Heng Henry H.-Q. , Chik Ki Wai , Shi Xiao-Mei , Tsui Lap-Chee , Cheng Shuk Han , Joyner Alexandra L. , Hui Chi-chung 
Published: April 2021

ABSTRACT
The correct patterning of vertebrate skeletal elements is controlled by inductive interactions. Two vertebrate hedgehog proteins, Sonic hedgehog and Indian hedgehog, have been implicated in skeletal development. During somite differentiation and limb development, Sonic hedgehog functions as an inductive signal from the notochord, floor plate and zone of polarizing activity. Later in skeletogenesis, Indian hedgehog functions as a regulator of chondrogenesis during endochondral ossification. The vertebrate Gli zinc finger proteins are putative transcription factors that respond to Hedgehog signaling. In Drosophila, the Gli homolog cubitus interruptus is required for the activation of hedgehog targets and also functions as a repressor of hedgehog expression. We show here that Gli2 mutant mice exhibit severe skeletal abnormalities including cleft palate, tooth defects, absence of vertebral body and intervertebral discs, and shortened limbs and sternum. Interestingly, Gli2 and Gli3 (C.-c. Hui and A. L. Joyner (1993). Nature Genet. 3, 241-246) mutant mice exhibit different subsets of skeletal defects indicating that they implement specific functions in the development of the neural crest, somite and lateral plate mesoderm derivatives. Although Gli2 and Gli3 are not functionally equivalent, double mutant analysis indicates that, in addition to their specific roles, they also serve redundant functions during skeletal development. The role of Gli2 and Gli3 in Hedgehog signaling during skeletal development is discussed.
Multiple signaling events specify ectoderm and pattern the oral-aboral axis in the sea urchin embryo
Authors: Wikramanayake Athula H. , Klein William H. 
Published: April 2021

ABSTRACT
In the sea urchin embryo, the animal-vegetal axis is established during oogenesis and the oral-aboral axis is specified sometime after fertilization. The mechanisms by which either of these axes are specified and patterned during embryogenesis are poorly understood. Here, we investigated the role of cellular interactions in the specification of the ectoderm territories and polarization of the ectoderm along the oral-aboral axis. Isolated animal halves (mesomeres), which are fated to give rise to oral and aboral ectoderm, developed into polarized embryoids that expressed an oral ectoderm-specific marker uniformly. These embryoids also produced neuron-like cells and serotonergic neurons, suggesting that mesomeres are autonomously specified as oral ectoderm. Mesomere-derived embryoids did not express any aboral ectodermspecific markers, although we previously showed that aboral ectoderm-specific genes can be induced by 25 mM lithium chloride, which also induced endoderm formation (Wikramanayake, A. H., Brandhorst, B. P. and Klein, W. H. (1995). Development 121, 1497-1505). To ascertain if endoderm formation is a prerequisite for induction of aboral ectoderm by lithium and for normal ectoderm patterning in animal halves, we modulated the lithium treatment to ensure that no endoderm formed. Remarkably, treating animal halves with 10 mM LiCl at ∼7 hours postfertilization resulted in embryoids that displayed oralaboral axis patterning in the absence of endoderm. Application of 25 mM LiCl to animal halves at ∼16 hours postfertilization, which also did not induce endoderm, resulted in polarized expression of the aboral ectoderm-specific LpS1 protein, but global expression of the Ecto V antigen and no induction of the stomodeum or ciliary band. These results suggest that at least two signals, a positive inductive signal to specify the aboral ectoderm and a negative suppressive signal to inactivate oral ectoderm-specific genes in the prospective aboral ectoderm territory, are needed for correct spatial expression of oral and aboral ectodermspecific genes. Transmission of both these signals may be prerequisite for induction of secondary ectodermal structures such as the ciliary band and stomodeum. Thus, differentiation of ectoderm and polarization of the oral-aboral axis in Lytechinus pictus depends on cellular interactions with vegetal blastomeres as well as interactions along the oral-aboral axis.
Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and morphogenesis
Authors: Bellusci Savério , Furuta Yasuhide , Rush Margaret G. , Henderson Randall , Winnier Glenn , Hogan Brigid L. M. 
Published: April 2021

ABSTRACT
Branching morphogenesis of the embryonic lung requires interactions between the epithelium and the mesenchyme. Previously, we reported that Sonic hedgehog (Shh) transcripts are present in the epithelium of the developing mouse lung, with highest levels in the terminal buds. Here, we report that transcripts of mouse patched (Ptc), the homologue of a Drosophila gene encoding a putative transmembrane protein required for hedgehog signaling, are expressed at high levels in the mesenchyme adjacent to the end buds. To investigate the function of SHH in lung development, Shh was overexpressed throughout the distal epithelium, using the surfactant protein-C (SP-C) enhancer/promoter. Beginning around 16.5 dpc, when Shh and Ptc RNA levels are normally both declining, this treatment caused an increase in the ratio of interstitial mesenchyme to epithelial tubules in transgenic compared to normal lungs. Transgenic newborn mice die soon after birth. Histological analysis of the lungs at the light and electron microscope level shows an abundance of mesenchyme and the absence of typical alveoli. In vivo BrdU labeling indicates that Shh overexpression results in increased mesenchymal and epithelial cell proliferation at 16.5 and 17.5 dpc. However, analysis of CC-10 and SP-C expression reveals no significant inhibition in the differentiation of proximal and distal epithelial cells. The expression of genes potentially regulated by SHH was also examined. No difference could be observed between transgenic and control lungs in either the level or distribution of Bmp4, Wnt2 and Fgf7 RNA. By contrast, Ptc is clearly upregulated in the transgenic lung. These results thus establish a role for SHH in lung morphogenesis, and suggest that SHH normally regulates lung mesenchymal cell proliferation in vivo.
ladybird, a tandem of homeobox genes that maintain late wingless expression in terminal and dorsal epidermis of the Drosophila embryo
Authors: Jagla Krzysztof , Jagla Teresa , Heitzler Pascal , Dretzen Guy , Bellard François , Bellard Maria 
Published: April 2021

ABSTRACT
ladybird early and ladybird late genes, tandemly located in the Drosophila 93E homeobox gene cluster, encode highly related homeodomain-containing transcription factors. Here we report the cloning of the complete cDNA sequences of both genes and a study of their expression and regulatory interactions with the segment polarity gene wingless in the epidermis. ladybird genes are co-expressed with wingless in epidermal cells close to the posterior parasegmental boundaries and in terminal regions of the body. In mutant embryos with altered wingless function, transcription of ladybird early and ladybird late is changed; it disappears completely from the epidermis in wingless− embryos, indicating wingless-dependence. After 6 hours of development, wingless expression is maintained by gooseberry in the ventral epidermis. However, in the dorsal epidermis and the terminal regions of the body, expression of wingless is independent of gooseberry but requires a wingless-ladybird regulatory feedback loop. Loss of ladybird function reduces the number of wingless-expressing cells in dorsal epidermis and leads to complete inactivation of wingless in the anal plate. Consequently, mutant ladybird embryos fail to develop anal plates and ubiquitous embryonic expression of either one or both ladybird genes leads to severe defects of the dorsal cuticle. Lack of late wingless expression and anal plate formation can be rescued with the use of a heat-shock-ladybird transgene.
Requirements of DFR1/Heartless, a mesoderm-specific Drosophila FGF-receptor, for the formation of heart, visceral and somatic muscles, and ensheathing of longitudinal axon tracts in CNS
Authors: Shishido Emiko , Ono Naotaka , Kojima Tetsuya , Saigo Kaoru 
Published: April 2021

ABSTRACT
DFR1 encodes a mesoderm-specific fibroblast growth factor receptor in Drosophila. Here, we identified and characterized a protein-null mutant of DFR1 and examined DFR1 expression in embryos using anti-DFR1 antibody. Mutant phenotypes were completely rescued by a genomic fragment from the DFR1 locus. After invagination, mesodermal cells expressing DFR1 undergo proliferation and spread out dorsally to form a monolayer beneath the ectoderm. In mutant embryos, however, the mesoderm is not capable of extending to the normal dorsal limit and consequently mesodermal cells fail to receive ectodermal signals and thus rendered incapable of differentiating into primordia for the heart, visceral and somatic muscles. DFR1 is also required for normal development of the central nervous system. The absence of DFR1 resulted in the failure of longitudinal glia to enwrap longitudinal axon tracts. DFR1 mutant phenotypes were partially mimicked by the targeted expression of activated Yan, thus demonstrating the MAP kinase pathway to be involved in differentiation of mesoderm.
Transcriptionally repressed germ cells lack a subpopulation of phosphorylated RNA polymerase II in early embryos of Caenorhabditis elegans and Drosophila melanogaster
Authors: Seydoux Geraldine , Dunn Melanie A. 
Published: April 2021

ABSTRACT
Early embryonic germ cells in C. elegans and D. melanogaster fail to express many messenger RNAs expressed in somatic cells. In contrast, we find that ribosomal RNAs are expressed in both cell types. We show that this deficiency in mRNA production correlates with the absence of a specific phosphoepitope on the carboxyterminal domain of RNA polymerase II. In both C. elegans and Drosophila embryos, this phosphoepitope appears in somatic nuclei coincident with the onset of embryonic transcription, but remains absent from germ cells until these cells associate with the gut primordium during gastrulation. In contrast, a second distinct RNA polymerase II phosphoepitope is present continuously in both somatic and germ cells. The germ-line-specific factor PIE-1 is required to block mRNA production in the germ lineage of early C. elegans embryos (Seydoux, G., Mello, C. C., Pettitt, J., Wood, W. B., Priess, J. R. and Fire, A. (1996)Nature 382, 713-716). We show here that PIE-1 is also required for the germ-line-specific pattern of RNA polymerase II phosphorylation. These observations link inhibition of mRNA production in embryonic germ cells to a specific modification in the phosphorylation pattern of RNA polymerase II and suggest that repression of RNA polymerase II activity may be part of an evolutionarily conserved mechanism that distinguishes germ line from soma during early embryogenesis. In addition, these studies also suggest that different phosphorylated isoforms of RNA polymerase II perform distinct functions.
A novel fibroblast growth factor gene expressed in the developing nervous system is a downstream target of the chimeric homeodomain oncoprotein E2A-Pbx1
Authors: McWhirter John R. , Goulding Martyn , Weiner Joshua A. , Chun Jerold , Murre Cornelis 
Published: April 2021

ABSTRACT
Pbx1 is a homeodomain transcription factor that has the ability to form heterodimers with homeodomain proteins encoded by the homeotic selector (Hox) gene complexes and increase their DNA-binding affinity and specificity. A current hypothesis proposes that interactions with Pbx1 are necessary for Hox proteins to regulate downstream target genes that in turn control growth, differentiation and morphogenesis during development. In pre B cell leukemias containing the t(1;19) chromosome transloca-tion, Pbx1 is converted into a strong transactivator by fusion to the activation domain of the bHLH transcription factor E2A. The E2A-Pbx1 fusion protein should therefore activate transcription of genes normally regulated by Pbx1. We have used the subtractive process of representational difference analysis to identify targets of E2A-Pbx1. We show that E2A-Pbx1 can directly activate transcription of a novel member of the fibroblast growth factor family of intercellular signalling molecules, FGF-15. The FGF-15 gene is expressed in a regionally restricted pattern in the developing nervous system, suggesting that FGF-15 may play an important role in regulating cell division and pat-terning within specific regions of the embryonic brain, spinal cord and sensory organs.
Targeted neuronal ablation: the role of pioneer neurons in guidance and fasciculation in the CNS of Drosophila
Authors: Hidalgo A. , Brand A. H. 
Published: April 2021

ABSTRACT
Although pioneer neurons are the first to delineate the axon pathways, it is uncertain whether they have unique pathfinding abilities. As a first step in defining the role of pioneer neurons in the Drosophila embryonic CNS, we describe the temporal profile and trajectory of the axons of four pioneer neurons and show that they differ from previously published reports. We show, by targeted ablation of one, two, three or four pioneer neurons at a time, that (1) no single pioneer neuron is essential for axon tract formation, (2) the interaction between two pioneers is necessary for the establishment of each fascicle and (3) pioneer neurons function synergistically to establish the longitudinal axon tracts, to guide the fasciculation of follower neurons along specific fascicles and to prevent axons from crossing the midline.
Feedback regulation is central to Delta-Notch signalling required for Drosophila wing vein morphogenesis
Authors: Huppert Stacey S. , Jacobsen Thomas L. , Muskavitch Marc A. T. 
Published: April 2021

ABSTRACT
Delta and Notch are required for partitioning of vein and intervein cell fates within the provein during Drosophila metamorphosis. We find that partitioning of these fates is dependent on Delta-mediated signalling from 22 to 30 hours after puparium formation at 25°C. Within the provein, Delta is expressed more highly in central provein cells (presumptive vein cells) and Notch is expressed more highly in lateral provein cells (presumptive intervein cells). Accumulation of Notch in presumptive intervein cells is dependent on Delta signalling activity in presumptive vein cells and constitutive Notch receptor activity represses Delta accumulation in presumptive vein cells. When Delta protein expression is elevated ectopically in presumptive intervein cells, complementary Delta and Notch expression patterns in provein cells are reversed, and vein loss occurs because central provein cells are unable to stably adopt the vein cell fate. Our findings imply that Delta-Notch signalling exerts feedback regulation on Delta and Notch expression during metamorphic wing vein development, and that the resultant asymmetries in Delta and Notch expression underlie the proper specification of vein and intervein cell fates within the provein.
The induction and maintenance of flowering in Impatiens
Authors: Pouteau Sylvie , Nicholls David , Tooke Fiona , Coen Enrico , Battey Nicholas 
Published: April 2021

ABSTRACT
The mechanisms that establish the floral meristem are now becoming clearer, but the way in which flowering is maintained is less well understood. Impatiens balsamina provides a unique opportunity to address this question because reversion to vegetative growth can be obtained in a predictable way by transferring plants from inductive to non-inductive conditions. Following increasing amounts of induction, reversion takes place at progressively later stages of flower development. Partial flower induction and defoliation experiments show that a floral signal is produced in the cotyledon in response to inductive con-ditions and that this signal progressively diminishes after transfer to non-inductive conditions, during reversion. Therefore reversion in Impatiens is most likely due to the failure of leaves to become permanent sources of inductive signal in addition to the lack of meristem commitment to flowering. Analysis of the expression of the Impatiens homologues of the meristem identity genes floricaula and squamosa indicates that a change in floricaula transcription is not associated with the establishment or maintenance of the floral meristem in this species. Squamosa transcription is associated with floral development and petal initiation, and is maintained in existing petal or petaloid primordia even after the meristem has reverted. However, it is not expressed in the reverted meristem, in which leaves are initiated in whorled phyllotaxis and without axillary meristems, both characteristics usually associated with the floral meristem. These observations show that squamosa expression is not needed for the maintenance of these floral characters. The requirement for the production of the floral signal in the leaf during the process of flower development may reflect an additional function separate to that of squamosa activation; alternatively the signal may be required to ensure continued transcriptional activation in the meristem.
Secreted forms of DELTA and SERRATE define antagonists of Notch signaling in Drosophila
Authors: Sun Xin , Artavanis-Tsakonas Spyros 
Published: April 2021

ABSTRACT
We examined the function of secreted forms of the two known Drosophila Notch ligands, DELTA and SERRATE, by expressing them under various promoters in the Drosophila developing eye and wing. The phenotypes associated with the expression of secreted Delta (DlS) or secreted Serrate (SerS) forms mimic loss-of-function mutations in the Notch pathway. Both genetic interactions between DlS or SerS transgenics and duplications or loss-of-function mutations of Delta or Serrate indicate that DlS and SerS behave as dominant negative mutations. These observations were extended to the molecular level by demonstrating that the expression of Enhancer of split mδ, a target of Notch signaling, is down-regulated by SERS. The antagonistic nature of the two mutant secreted ligand forms in the eye is consistent with their behavior in the wing, where they are capable of down-regulating wing margin specific genes opposite to the effects of the endogenous ligands. This analysis uncovers secreted molecular antagonists of Notch signaling and provides evidence of qualitative differences in the actions of the two ligands DLS and SERS.
Synergistic interactions between bFGF and a TGF-β family member may mediate myogenic signals from the neural tube
Authors: Stern Howard M. , Lin-Jones Jennifer , Hauschka Stephen D. 
Published: April 2021

ABSTRACT
Development of the myotome within somites depends on unknown signals from the neural tube. The present study tested the ability of basic fibroblast growth factor (bFGF), transforming growth factor-β1 (TGF-β1) and dorsalin-1 (dsl-1) to promote myogenesis in stage 10-14 chick paraxial mesoderm utilizing 72 hour explant cultures. Each of these factors alone and the combination of bFGF with dsl-1 had limited to no myogenic-promoting activity, but the combination of bFGF with TGF-β1 demonstrated a potent dose-dependent effect. In addition, bFGF enhanced the survival/proliferation of somite cells. 98% of stage 10-11 caudal segmental plate explants treated with bFGF plus TGF-β1, exhibited myosin heavy chain (MHC)-positive cells (avg.=60 per explant), whereas only 15% of similarly treated somites responded with an average of 5 MHC-positive cells. Thus at stage 10-11, there are rostrocaudal differences in myogenic responsiveness with the caudal (more ‘immature’) paraxial mesoderm being more myogenically responsive to these factors than are somites. It was also discovered that 17% of stage 10-11 caudal segmental plate explants exhibited several MHC-positive cells even when cultured without added growth factors, further demonstrating a different myogenic potential of the caudal paraxial mesoderm. Stage 13-14 paraxial mesoderm also exhibited a myogenic response to bFGF/TGF-β1 but, unlike stage 10-11 embryos, both somites and segmental plate exhibited a strong response. A two-step mechanism for the bFGF/TGF-β1 effect is suggested by the finding that only TGF-β1 was required during the first 12 hours of culture, whereas bFGF plus a TGF-β-like factor were required for the remainder of the culture. The biological relevance of the findings with bFGF is underscored by the observation that a monoclonal antibody to bFGF inhibited myogenic signaling from the dorsal neural tube. However, a monoclonal antibody that can neutralize the three factors TGF-β1, TGF-β2 and TGF-β3 did not block myogenic signals from the neural tube, raising the possibility that another TGF-β family member may be involved in vivo.
Isoform-specific expression and function of neuregulin
Authors: Meyer Dirk , Yamaai Tomoichiro , Garratt Alistair , Riethmacher-Sonnenberg Eva , Kane Darci , Theill Lars E. , Birchmeier Carmen 
Published: April 2021

ABSTRACT
Neuregulin (also known as NDF, heregulin, ARIA, GGF or SMDF), induces cell growth and differentiation. Biological effects of neuregulin are mediated by members of the erbB family of tyrosine kinase receptors. Three major neuregulin isoforms are produced from the gene, which differ substantially in sequence and in overall structure. Here we use in situ hybridization with isoform-specific probes to illustrate the spatially distinct patterns of expression of the isoforms during mouse development. Ablation of the neuregulin gene in the mouse has demonstrated multiple and independent functions of this factor in development of both the nervous system and the heart. We show here that targeted mutations that affect different isoforms result in distinct phenotypes, demonstrating that isoforms can take over specific functions in vivo. Type I neuregulin is required for generation of neural crest-derived neurons in cranial ganglia and for trabeculation of the heart ventricle, whereas type III neuregulin plays an important role in the early development of Schwann cells. The complexity of neuregulin functions in development is therefore due to independent roles played by distinct isoforms.