bluuebunny/crossref_metadata_2025_split huggingface dataset:
slimb coordinates wg and dpp expression in the dorsal-ventral and anterior-posterior axes during limb development
Authors: Theodosiou Nicole A. , Zhang Sheng , Wang Wei-Yi , Xu Tian 
Published: April 2021

ABSTRACT
In the Drosophila leg disc, wingless (wg) and decapentaplegic (dpp) are expressed in a ventral-anterior and dorsal-anterior stripe of cells, respectively. This pattern of expression is essential for proper limb development. While the Hedgehog (Hh) pathway regulates dpp and wg expression in the anterior-posterior (A/P) axis, mechanisms specifying their expression in the dorsal-ventral (D/V) axis are not well understood. We present evidence that slimb mutant clones in the disc deregulate wg and dpp expression in the D/V axis. This suggests for the first time that their expression in the D/V axis is actively regulated during imaginal disc development. Furthermore, slimb is unique in that it also deregulates wg and dpp in the A/P axis. The misexpression phenotypes of slimb− clones indicate that the regulation of wg and dpp expression is coordinated in both axes, and that slimb plays an essential role in integrating A/P and D/V signals for proper patterning during development. Our genetic analysis further reveals that slimb intersects the A/P pathway upstream of smoothened (smo).
The iroquois complex controls the somatotopy of Drosophila notum mechanosensory projectionss
Authors: Grillenzoni Nicola , Helden Jacques van , Dambly-Chaudière Christine , Ghysen Alain 
Published: April 2021

ABSTRACT
Sensory neurons can establish topologically ordered projections in the central nervous system, thereby building an internal representation of the external world. We analyze how this ordering is genetically controlled in Drosophila, using as a model system the neurons that innervate the mechanosensory bristles on the back of the fly (the notum). Sensory neurons innervating the medially located bristles send an axonal branch that crosses the central nervous system midline, defining a ‘medial’ identity, while the ones that innervate the lateral bristles send no such branch, defining a ‘lateral’ identity. We analyze the role of the proneural genes achaete and scute, which are involved in the formation of the medial and lateral bristles, and we show that they have no effect on the ‘medial’ and ‘lateral’ identities of the neurons. We also analyze the role of the prepattern genes araucan and caupolican, two members of the iroquois gene complex which are required for the expression of achaete and scute in the lateral region of the notum, and we show that their expression is responsible for the ‘lateral’ identity of the projection.
A Drosophila RNA helicase gene, pitchoune, is required for cell growth and proliferation and is a potential target of d-Myc
Authors: Zaffran S. , Chartier A. , Gallant P. , Astier M. , Arquier N. , Doherty D. , Gratecos D. , Sémériva M. 
Published: April 2021

ABSTRACT
This article describes the characterization of a new Drosophila gene that we have called pitchoune (pit) (meaning small in Provence) because mutations in this gene produce larvae that cannot grow beyond the first instar larval stage although they can live as long as 7-10 days. All the tissues are equally affected and the perfectly shaped larvae are indistinguishable from first instar wild-type animals. Analysis of mutant somatic clones suggests a function in cell growth and proliferation, which is supported by the fact that cell proliferation is promoted by pit overexpression. Tagged-Pit, when transfected in S2 cells, localizes mainly to the nucleolus, pointing towards a possible role in ribosome biogenesis and, consequently, in protein biosynthesis. pit encodes a DEAD-box RNA helicase, a family of proteins involved in the control of RNA structure in many cellular processes and its closest homologue is a human DEAD-box RNA helicase, MrDb, whose corresponding gene transcription is directly activated by Myc-Max heterodimers (Grandori, C., Mac, J., Siëbelt, F., Ayer, D. E. and Eisenman, R. N. (1996) EMBO J. 15, 4344-4357). The patterns of expression of d-myc and pit are superimposable. Ectopic expression of myc in the nervous system drives an ectopic expression of pit in this tissue indicating that in Drosophila as well, pit is a potential target of d-Myc. These results suggest that myc might promote cell proliferation by activating genes that are required in protein biosynthesis, thus linking cell growth and cell proliferation.
A Serum Response Factor homolog is required for spore differentiation in Dictyostelium
Authors: Escalante Ricardo , Sastre Leandro 
Published: April 2021

ABSTRACT
A homolog of the Serum Response Factor (SRF) has been isolated from Dictyostelium discoideum and its function studied by analyzing the consequences of its gene disruption. The MADS-box region of Dictyostelium SRF (DdSRF) is highly conserved with those of the human, Drosophila and yeast homologs. srfA is a developmentally regulated gene expressed in prespore and spore cells. This gene plays an essential role in sporulation as its disruption leads to abnormal spore morphology and loss of viability. The mutant spores were round and cellulose deposition seemed to be partially affected. Initial prestalk and prespore cell differentiation did not seem to be compromised in the mutant since the expression of several cell-type-specific markers were found to be unaffected. However, the mRNA level of the spore marker spiA was greatly reduced. Activation of the cAMP-dependent protein kinase (PKA) by 8-Br-cAMP was not able to fully bypass the morphological defects of srfA− mutant spores, although this treatment induced spiA mRNA expression. Our results suggest that DdSRF is required for full maturation of spores and participates in the regulation of the expression of the spore-coat marker spiA and probably other maturation genes necessary for proper spore cell differentiation.
Developmental remodeling and shortening of the cardiac outflow tract involves myocyte programmed cell death
Authors: Watanabe Michiko , Choudhry Aleem , Berlan Michael , Singal Amishi , Siwik Ernest , Mohr Susanne , Fisher Steven A. 
Published: April 2021

ABSTRACT
The embryonic outflow tract is a simple tubular structure that connects the single primitive ventricle with the aortic sac and aortic arch arteries. This structure undergoes a complex sequence of morphogenetic processes to become the portion of the heart that aligns the right and left ventricles with the pulmonary artery and aorta. Abnormalities of the outflow tract are involved in many clinically significant congenital cardiac defects; however, the cellular and molecular processes governing the development of this important structure are incompletely understood. Histologic and tissue-tagging studies indicate that the outflow tract tissues compact and are incorporated predominantly into a region of the right ventricle. The hypothesis tested in the current study was that cell death or apoptosis in the muscular portion of the outflow tract is an important cellular mechanism for outflow tract shortening. The tubular outflow tract myocardium was specifically marked by infecting myocytes of the chicken embryo heart with a recombinant replication-defective adenovirus expressing β-galactosidase (β-gal) under the control of the cytomegalovirus promoter. Histochemical detection of the β-gal-labeled outflow tract myocytes revealed that the tubular structure shortened to become a compact ring at the level of the pulmonic infundibulum over several days of development (stages 25-32, embryonic days 4-8). The appearance of apoptotic cardiomyocytes was correlated with OFT shortening by two histologic assays, TUNEL labeling of DNA fragments and AnnexinV binding. The rise and fall in the number of apoptotic myocytes detected by histologic analyses paralleled the change in activity levels of Caspase-3, a protease in the apoptotic cascade, measured in outflow tract homogenates. These results suggest that the elimination of myocytes by programmed cell death is one mechanism by which the outflow tract myocardium remodels to form the proper connection between the ventricular chambers and the appropriate arterial trunks.
Generation of multiple antagonistic domains along the proximodistal axis during Drosophila leg development
Authors: Abu-Shaar Muna , Mann Richard S. 
Published: April 2021

ABSTRACT
homothorax (hth) is a Drosophila member of the Meis family of homeobox genes. hth function is required for the nuclear localization of the Hox cofactor Extradenticle (EXD). We show here that there is also a post-transcriptional control of HTH by exd: exd activity is required for the apparent stability of the HTH protein. In leg imaginal discs, hth expression is limited to the domain of exd function and this domain is complementary to the domain in which the Wingless (WG) and Decapentaplegic (DPP) signals are active. We demonstrate that WG and DPP act together through their targets Distal-less (Dll) and dachshund (dac) to restrict hth expression, and therefore EXD’s nuclear localization, to the most proximal regions of the leg disc. Furthermore, there is a reciprocal repression exerted by HTH on these and other DPP and WG downstream targets that restricts their expression to non-hth-expressing cells. Thus, there exists in the leg disc a set of mutually antagonistic interactions between proximal cells, which we define as those that express hth, and distal cells, or those that do not express hth. In addition, we show that dac negatively regulates Dll. We suggest that these antagonistic relationships help to convert the WG and DPP activity gradients into discreet domains of gene expression along the proximodistal axis.
Sperm-induced local[Ca2+]i rise separated from the Ca2+ wave in sea urchin eggs in the presence of a gamete fusion inhibitor, jaspisin
Authors: Mohri Tatsuma , Miyazaki Shunichi , Shirakawa Hideki , Ikegami Susumu 
Published: April 2021

ABSTRACT
An increase in intracellular Ca2+ concentration ([Ca2+]i) at a focal plane was recorded simultaneously with sperm-egg binding and membrane current upon insemination of sea urchin Hemicentrotus pulcherrimus eggs. No change in current and [Ca2+]i occurred in the presence of jaspisin, a novel substance that inhibits metallo-endoproteinase and sperm-egg membrane fusion (S. Ikegami, H. Kobayashi, Y. Myotoishi, S. Ohta and K. H. Kato (1994) J. Biol. Chem. 269, 23262-23267). With low doses of jaspisin, a spermatozoon first produced a step inward current (Ion) as an indication of gamete membrane fusion and then induced a local [Ca2+]i rise at the site of sperm attachment 6-10 seconds after Ion. The sperm, however, soon detached from the egg. Increasing inward current was abruptly cut off (Ioff) within 9-15 seconds and the local [Ca2+]i rise began to decline 1-3 seconds after Ioff. In most cases, no further responses or an elevation of fertilization envelope (FE) occurred. In some cases, [Ca2+]i at the sperm attachment site increased again even after the sperm detached and triggered a Ca2+ wave which caused an activation current and FE formation. This recording of a gamete membrane- fusion-induced local [Ca2+]i rise, separated from the Ca2+ wave, is a key phenomenon for elucidating the initial sperm stimulation of the egg at fertilization.
Lhx2, a vertebrate homologue of apterous, regulates vertebrate limb outgrowth
Authors: Rodriguez-Esteban Concepción , Schwabe John W. R. , Peña Jennifer De La , Rincon-Limas Diego E. , Magallón Jorge , Botas Juan , Izpisúa Belmonte Juan Carlos 
Published: April 2021

ABSTRACT
apterous specifies dorsal cell fate and directs outgrowth of the wing during Drosophila wing development. Here we show that, in vertebrates, these functions appear to be performed by two separate proteins. Lmx-1 is necessary and sufficient to specify dorsal identity and Lhx2 regulates limb outgrowth. Our results suggest that Lhx2 is closer to apterous than Lmx-1, yet, in vertebrates, Lhx2 does not specify dorsal cell fate. This implies that in vertebrates, unlike Drosophila, limb outgrowth can be dissociated from the establishment of the dorsoventral axis.
Requirement for Brn-3c in maturation and survival, but not in fate determination of inner ear hair cells
Authors: Xiang Mengqing , Gao Wei-Qiang , Hasson Tama , Shin Joyce J. 
Published: April 2021

ABSTRACT
Mutations in the POU domain gene Brn-3c causes hearing impairment in both the human and mouse as a result of inner ear hair cell loss. We show here that during murine embryogenesis, Brn-3c is expressed in postmitotic cells committed to hair cell phenotype but not in mitotic progenitors in the inner ear sensory epithelium. In developing auditory and vestibular sensory epithelia of Brn-3c−/− mice, hair cells are found to be generated and undergo initial differentiation as indicated by their morphology, laminar position and expression of hair cell markers, including myosins VI and VIIa, calretinin and parvalbumin. However, a small number of hair cells are anomalously retained in the supporting cell layer in the vestibular sensory epithelia. Furthermore, the initially differentiated hair cells fail to form stereociliary bundles and degenerate by apoptosis in the Brn-3c−/− mice. These data indicate a crucial role for Brn-3c in maturation, survival and migration of hair cells, but not in proliferation or commitment of hair cell progenitors.
The knirps and knirps-related genes organize development of the second wing vein in Drosophila
Authors: Lunde Karen , Biehs Brian , Nauber Ulrich , Bier Ethan 
Published: April 2021

ABSTRACT
The neighboring homologous knirps (kni) and knirpsrelated (knrl) genes in Drosophila encode transcription factors in the steroid hormone receptor superfamily. During early embryogenesis, kni functions as a gap gene to control expression of segmentation genes within the abdominal region of the embryo. In this study, we present evidence that kni and knrl link A/P positional information in larval wing imaginal discs to morphogenesis of the second longitudinal wing vein (L2). We show that kni and knrl are expressed in similar narrow stripes corresponding to the position of the L2 primordium. The kni and knrl L2 stripes abut the anterior border of the broad central expression domain of the Dpp target gene spalt major (salm). We provide evidence that radius incompletus (ri), a well-known viable mutant lacking the L2 vein, is a regulatory mutant of the kni/knrl locus. In ri mutant wing discs, kni and knrl fail to be expressed in the L2 primordium. In addition, the positions of molecular breakpoints in the kni/knrl locus indicate that the ri function is provided by cis-acting sequences upstream of the kni transcription unit. Epistasis tests reveal that the kni/knrl locus functions downstream of spalt major (salm) and upstream of genes required to initiate vein-versusintervein differentiation. Mis-expression experiments suggest that kni and knrl expressing cells inhibit neighboring cells from becoming vein cells. Finally, kni and knrl are likely to refine the L2 position by positively auto-regulating their own expression and by providing negative feedback to repress salm expression. We propose a model in which the combined activities of kni and knrl organize development of the L2 vein in the appropriate position.
The Drosophila Pax gene eye gone is required for embryonic salivary duct development
Authors: Jones Nikolas A. , Kuo Yien Ming , Sun Y. Henry , Beckendorf Steven K. 
Published: April 2021

ABSTRACT
What are the developmental mechanisms required for conversion of an undifferentiated, two-dimensional field of cells into a patterned, tubular organ? In this report, we describe the contribution of the Drosophila Pax gene eye gone to the development of the embryonic salivary glands and ducts. eye gone expression in salivary tissues is controlled by several known regulators of salivary fate. After the initial establishment of the salivary primordium by Sex combs reduced, fork head excludes eye gone expression from the pregland cells so that its salivary expression is restricted to the posterior preduct cells. trachealess, in contrast, activates eye gone expression in the posterior preduct cells. We have previously described the process by which fork head and the EGF receptor pathway define the border between the gland and duct primordia. Here we show that eye gone is required for the subdivision of the duct primordium itself into the posterior individual duct and the anterior common duct domains. In the absence of eye gone, individual ducts as well as the precursor of the adult salivary glands, the imaginal ring, are absent. We took advantage of this ductless phenotype to show that Drosophila larvae do not have an obligate requirement for salivary glands and ducts. In addition to its role in the salivary duct, eye gone is required in the embryo for the development of the eye-antennal imaginal disc and the chemosensory antennal organ.
Role of Dpp signalling in prepattern formation of the dorsocentral mechanosensory organ in Drosophila melanogaster
Authors: Tomoyasu Yoshinori , Nakamura Makoto , Ueno Naoto 
Published: April 2021

ABSTRACT
A proneural cluster of dorsocentral bristles forms adjacent to the dorsal side of wg-expressing cells in the notum region of the wing imaginal disc. It has been shown that wg activity is required for these structures to form. However, the restriction of this proneural cluster to the dorsal posterior side of the wg expression domain in the anterior compartment of the wing imaginal disc has suggested that Wg signalling itself is insufficient to establish the dorsocentral proneural cluster. Some factor(s) from the posterior side must participate in this action in cooperation with Wg signalling. We have examined the role of Dpp signalling in dorsocentral bristle formation by either ectopically activating or conditionally reducing Dpp signalling. Ubiquitous activation of Dpp signalling in the notum region of the wing imaginal disc induced additional dorsocentral proneural cluster all along the dorsal side of the wg expression domain, and altered wg expression. Conditional loss-of-function of Dpp signalling during disc development resulted in the inhibition of dorsocentral proneural cluster formation and expansion of the wg expression domain. These results suggest that Dpp signalling has two indispensable roles in dorsocentral bristle formation: induction of the dorsocentral proneural cluster in cooperation with Wg signalling and restriction of the wg expression domain in the notum region of the wing imaginal disc.
Semaphorins III and IV repel hippocampal axons via two distinct receptors
Authors: Chédotal Alain , Del Rio Jose A. , Ruiz Monica , He Zhigang , Borrell Victor , de Castro Fernando , Ezan Frédéric , Goodman Corey S. , Tessier-Lavigne Marc , Sotelo Constantino , Soriano Eduardo 
Published: April 2021

ABSTRACT
The semaphorins are the largest family of repulsive axon guidance molecules. Secreted semaphorins bind neuropilin receptors and repel sensory, sympathetic and motor axons. Here we show that CA1, CA3 and dentate gyrus axons from E15-E17 mouse embryo explants are selectively repelled by entorhinal cortex and neocortex. The secreted semaphorins Sema III and Sema IV and their receptors Neuropilin-1 and -2 are expressed in the hippocampal formation during appropriate stages. Sema III and Sema IV strongly repel CA1, CA3 and dentate gyrus axons; entorhinal axons are only repelled by Sema III. An antibody against Neuropilin-1 blocks the repulsive action of Sema III and the entorhinal cortex, but has no effect on Sema IV-induced repulsion. Thus, chemorepulsion plays a role in axon guidance in the hippocampus, secreted semaphorins are likely to be responsible for this action, and the same axons can be repelled by two distinct semaphorins via two different receptors.
not really finished is crucial for development of the zebrafish outer retina and encodes a transcription factor highly homologous to human Nuclear Respiratory Factor-1 and avian Initiation Binding Repressor
Authors: Becker Thomas S. , Burgess Shawn M. , Amsterdam Adam H. , Allende Miguel L. , Hopkins Nancy 
Published: April 2021

ABSTRACT
Not really finished (nrf), a larval-lethal mutation in zebrafish generated by retroviral insertion, causes specific retinal defects. Analysis of mutant retinae reveals an extensive loss of photoreceptors and their precursors around the onset of visual function. These neurons undergo apoptosis during differentiation, affecting all classes of photoreceptors, suggesting an essential function of nrf for the development of all types of photoreceptors. In the mutant, some photoreceptors escape cell death, are functional and, as judged by opsin expression, belong to at least three classes of cones and one class of rods. The protein encoded by nrf is a close homologue of human Nuclear Respiratory Factor 1 and avian Initiation Binding Repressor, transcriptional regulators binding the upstream consensus sequence RCGCRYGCGY. At 24 hours of development, prior to neuronal differentiation, nrf is expressed ubiquitously throughout the developing retina and central nervous system. At 48 hours of development, expression of nrf is detected in the ganglion cell layer, in the neurons of the inner nuclear layer, and in the optic nerve and optic tracts, and, at 72 hours of development, is no longer detectable by in situ hybridization. Mutants contain no detectable nrf mRNA and die within 2 weeks postfertilization as larvae with reduced brain size. On the basis of its similarity with NRF-1 and IBR, nrf is likely involved in transcriptional regulation of multiple target genes, including those that encode mitochondrial proteins, growth factor receptors and other transcription factors. This demonstrates the power of insertional mutagenesis as a means for characterizing novel genes necessary for vertebrate retinal development.
Heartbroken is a specific downstream mediator of FGF receptor signalling in Drosophila
Authors: Michelson Alan M. , Gisselbrecht Stephen , Buff Eugene , Skeath James B. 
Published: April 2021

ABSTRACT
Drosophila possesses two FGF receptors which are encoded by the heartless and breathless genes. HEARTLESS is essential for early migration and patterning of the embryonic mesoderm, while BREATHLESS is required for proper branching of the tracheal system. We have identified a new gene, heartbroken, that participates in the signalling pathways of both FGF receptors. Mutations in heartbroken are associated with defects in the migration and later specification of mesodermal and tracheal cells. Genetic interaction and epistasis experiments indicate that heartbroken acts downstream of the two FGF receptors but either upstream of or parallel to RAS1. Furthermore, heartbroken is involved in both the HEARTLESS- and BREATHLESS-dependent activation of MAPK. In contrast, EGF receptor-dependent embryonic functions and MAPK activation are not perturbed in heartbroken mutant embryos. A strong heartbroken allele also suppresses the effects of hyperactivated FGF but not EGF receptors. Thus, heartbroken may contribute to the specificity of developmental responses elicited by FGF receptor signalling.