bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of AmphiHox-1 and AmphiPax-1 in amphioxus embryos treated with retinoic acid: insights into evolution and patterning of the chordate nerve cord and pharynx
Authors: Holland Linda Z. , Holland Nicholas D. 
Published: April 2021

ABSTRACT
Excess all-trans retinoic acid (RA) causes severe craniofacial malformations in vertebrate embryos: pharyngeal arches are fused or absent, and a rostrad expansion of Hoxb-1 expression in the hindbrain shows that anterior rhombomeres are homeotically respecified to a more posterior identity. As a corollary, neural crest migration into the pharyngeal arches is abnormal. We administered excess RA to developing amphioxus, the closest invertebrate relative of the vertebrates and thus a key organism for understanding evolution of the vertebrate body plan. In normal amphioxus, the nerve cord has only a slight anterior swelling, the cerebral vesicle, and apparently lacks migratory neural crest. Nevertheless, excess RA similarly affects amphioxus and vertebrates. The expression domain of AmphiHox-1 (homologous to mouse Hoxb-1) in the amphioxus nerve cord is also extended anteriorly. For both the amphioxus and mouse genes, excess RA causes either (1) continuous expression throughout the preotic hindbrain (mouse) and from the level of somite 7 to the anterior end of the nerve cord (amphioxus) or (2) discontinuous expression with a gap in rhombomere 3 (mouse) and a gap at the posterior end of the cerebral vesicle (amphioxus). A comparison of these expression patterns suggests that amphioxus has a homolog of the vertebrate hindbrain, both preotic and postotic. Although RA alters the expression of AmphiHox-1 expression in the amphioxus nerve cord, it does not alter the expression of AmphiHox-1 in presomitic mesoderm or of alkali myosin light chain (AmphiMlc-alk) in somites, and the axial musculature and notochord develop normally. The most striking morphogenetic effect of RA on amphioxus larvae is the failure of mouth and gill slits to form. In vertebrates effects of excess RA on pharyngeal development have been attributed solely to the abnormal migratory patterns of Hox-expressing cranial neural crest cells. This cannot be true for amphioxus because of the lack of migratory neural crest. Furthermore, expression of Hox genes in pharyngeal tissues of amphioxus has not yet been detected. However, the absence of gill slits in RA-treated amphioxus embryos correlates with an RA-induced failure of AmphiPax-1 to become down-regulated in regions of pharyngeal endoderm that would normally fuse with the overlying ectoderm. In vertebrates, RA might similarly act via Pax-1/9, also expressed in pharyngeal endoderm, to impair pharyngeal patterning.
Renal agenesis and hypodysplasia in ret-k
– mutant mice result from defects in ureteric bud development
Authors: Schuchardt Anita , D’Agati Vivette , Pachnis Vassilis , Costantini Frank 
Published: April 2021

ABSTRACT
The c-ret gene encodes a receptor tyrosine kinase that is expressed in the Wolffian duct and ureteric bud of the developing excretory system. Newborn mice homozygous for a mutation in c-ret displayed renal agenesis or severe hypodysplasia, suggesting a critical role for this gene in metanephric kidney development. To investigate the embryological basis of these defects, we characterized the early development of the excretory system in mutant homozygotes, and observed a range of defects in the formation, growth and branching of the ureteric bud, which account for the spectrum of renal defects seen at birth. Co-culture of isolated ureteric buds and metanephric mesenchyme show that the primary defect is intrinsic to the ureteric bud. While the mutant bud failed to respond to induction by wild-type mesenchyme, mutant mesenchyme was competent to induce the growth and branching of the wild-type bud. Furthermore, the mutant metanephric mesenchyme displayed a normal capacity to differentiate into nephric tubules when co-cultured with embryonic spinal cord. These findings suggest a model in which c-ret encodes the receptor for a (yet to be identified) factor produced by the metanephric mesenchyme, which mediates the inductive effects of this tissue upon the ureteric bud. This factor appears to stimulate the initial evagination of the ureteric bud from the Wolffian duct, as well as its subsequent growth and branching.
Degeneration of vestibular neurons in late embryogenesis of both heterozygous and homozygous BDNF null mutant mice
Authors: Bianchi Lynne M. , Conover Joanne C. , Fritzsch Bernd , DeChiara Thomas , Lindsay Ronald M. , Yancopoulos George D. 
Published: April 2021

ABSTRACT
The generation of mice lacking specific neurotrophins permits evaluation of the trophic requirements of particular neuronal populations throughout development. In the present study, we examined the developing vestibulo-cochlear system to determine the time course of neurotrophin dependence and to determine whether competition occurred among developing cochlear or vestibular neurons for available amounts of either brain-derived neurotrophic factor (BDNF) or neurotrophin-4/5 (NT-4/5). Both cochlear and vestibular neurons were present in mice lacking NT-4/5. In contrast, vestibular neurons decreased in number beginning at mid-stages of inner ear development, in mice lacking BDNF. Early in development (E12.5-13), the size of the vestibular ganglion was normal in bdnf−/− mice. Decreased innervation to vestibular sensory epithelia was detected at E13.5-15, when progressive loss of all afferent innervation to the semicircular canals and reduced innervation to the utricle and saccule were observed. At E16.5-17, there was a reduction in the number of vestibular neurons in bdnf−/− mice. A further decrease in vestibular neurons was observed at P1 and P15. Compared to bdnf−/− mice, mice heterozygous for the BDNF null mutation (bdnf+/−) showed an intermediate decrease in the number of vestibular neurons from E16.5-P15. These data indicate a late developmental requirement of vestibular neurons for BDNF and suggest competition among these neurons for limited supplies of this factor.
Maturation Promoting Factor in ascidian oocytes is regulated by different intracellular signals at meiosis I and II
Authors: Russo Gian Luigi , Kyozuka Keiichiro , Antonazzo Livio , Tosti Elisabetta , Dale Brian 
Published: April 2021

ABSTRACT
Using the fluorescent dye Calcium Green-dextran, we measured intracellular Ca2+ in oocytes of the ascidian Ciona intestinalis at fertilization and during progression through meiosis. The relative fluorescence intensity increased shortly after insemination in a single transient, the activation peak, and this was followed by several smaller oscillations that lasted for approximately 5 minutes (phase 1). The first polar body was extruded after the completion of the phase 1 transients, about 9 minutes after insemination, and then the intracellular calcium level remained at baseline for a period of 5 minutes (phase 2). At 14 minutes postinsemination a second series of oscillations was initiated that lasted 11 minutes (phase 3) and terminated at the time of second polar body extrusion. Phases 1 and 3 were inhibited by preloading oocytes with 5 mM heparin. Simultaneous measurements of membrane currents, in the whole-cell clamp configuration, showed that the 1–2 nA inward fertilization current correlated temporally with the activation peak, while a series of smaller oscillations of 0.1–0.3 nA amplitude were generated at the time of the phase 3 oscillations.
Biochemical characterization of Maturation Promoting Factor (MPF) in ascidian oocytes led to the identification of a Cdc2-like kinase activity. Using p13suc1-sepharose as a reagent to precipitate the MPF complex, a 67 kDa (67×103Mr) protein was identified as cyclin B. Histone H1 kinase activity was high at metaphase I and decreased within 5 minutes of insemination reaching a minimum level during phase 2, corresponding to telophase I. During phase 3, H1 kinase activity increased and then decayed again during telophase II. Oocytes preloaded with BAPTA and subsequently inseminated did not generate any calcium transients, nonetheless H1 kinase activity decreased 5 minutes after insemination, as in the controls, and remained low for at least 30 minutes. Injection of BAPTA during phase 2 suppressed the phase 3 calcium transients, and inhibited both the increase in H1 kinase activity normally encountered at metaphase II and second polar body extrusion.
NF-κB activity in transgenic mice: developmental regulation and tissue specificity
Authors: Schmidt-Ullrich Ruth , Mémet Sylvie , Lilienbaum Alain , Feuillard Jean , Raphaël Martine , Israël Alain 
Published: April 2021

ABSTRACT
The transcription factor family NF-κB/Rel is responsible for the regulation of a large number of cellular genes and some viruses. Since there is a strong similarity between the NF-κB/Rel family members and the Drosophila melanogaster protein DORSAL, which is activated early during embryogenesis, we were interested in determining the pattern of NF-κB activity during mouse development. Two lacZ reporter constructs, each driven by promoter elements that are dependent on the presence of nuclear NF-κB/Rel activity, were used to produce transgenic mice. The analysis of these mice did not identify nuclear NF-κB/Rel activity in early development prior to implantation or during the gastrulation processes. Earliest expression of the lacZ transgene was detected on day E12.5. Before birth lacZ expression was seen in discrete regions of the rhombencephalon of the developing brain, in the spinal medulla, in some of the blood vessels and in the thymus. After birth, the NF-κB/Rel activity in the thymus remained but nuclear activity was also found in the bone marrow, in the spleen and in the capsule of the lymph nodes. In the central nervous system, drastic changes in NF-κB/Rel activity could be observed in the first 3 weeks after birth, when the cortex and the cerebellum reach functional and morphological maturity. Considering the results of the p50, p65, relB and c-rel knock-out mice and our present findings, we believe that the NF-κB/Rel proteins known so far are probably not implicated in processes of early development and differentiation of the different tissues, but rather in maintaining their function once matured.
E(z): a polycomb group gene or a trithorax group gene?
Authors: LaJeunesse Dennis , Shearn Allen 
Published: April 2021

ABSTRACT
The products of the Polycomb group of genes are cooperatively involved in repressing expression of homeotic selector genes outside of their appropriate anterior/posterior boundaries. Loss of maternal and/or zygotic function of Polycomb group genes results in the ectopic expression of both Antennapedia Complex and Bithorax Complex genes. The products of the trithorax group of genes are cooperatively involved in maintaining active expression of homeotic selector genes within their appropriate anterior/posterior boundaries. Loss of maternal and/or zygotic function of trithorax group genes results in reduced expression of both Antennapedia Complex and Bithorax Complex genes. Although Enhancer of zeste has been classified as a member of the Polycomb group, in this paper we show that Enhancer of zeste can also be classified as a member of the trithorax group. The requirement for Enhancer of zeste activity as either a trithorax group or Polycomb group gene depends on the homeotic selector gene locus as well as on spatial and temporal cues.
Identified central neurons convey a mitogenic signal from a peripheral target to the CNS
Authors: Becker Thomas S. , Bothe Gerald , Berliner Alyson J. , Macagno Eduardo R. 
Published: April 2021

ABSTRACT
Regulation of central neurogenesis by a peripheral target has been previously demonstrated in the ventral nerve cord of the leech Hirudo medicinalis (Baptista, C. A., Gershon, T. R. and Macagno, E. R. (1990). Nature 346, 855-858) Specifically, innervation of the male genitalia by the fifth and sixth segmental ganglia (the sex ganglia) was shown to trigger the birth of several hundred central neurons (PIC neurons) in these ganglia. As reported here, removal of the target early during induction shows that PIC neurons can be independently induced in each side of a ganglion, indicating that the inductive signal is both highly localized and conveyed to each hemiganglion independently. Further, since recent observations (Becker, T., Berliner, A. J., Nitabach, M. N., Gan, W.-B. and Macagno, E. R. (1995). Development, 121, 359-369) had indicated that efferent projections are probably involved in this phenomenon, we individually ablated all possible candidates, which led to the identification of two central neurons that appear to play significant roles in conveying the inductive signal to the CNS. Ablation of a single ML neuron reduced cell proliferation in its own hemiganglion by nearly 50%, on the average. In contrast, proliferation on the opposite side of the ganglion increased by about 25%, suggesting the possibility of a compensatory response by the remaining contralateral ML neuron. Simultaneous ablation of both ML neurons in a sex ganglion caused similar reductions in cell proliferation in each hemiganglion. Deletion of a single AL neuron produced a weaker (7%) but nonetheless reproducible reduction. Ablation of the other nine central neurons that might have been involved in PIC neuron induction had no detectable effect. Both ML and AL neurons exhibit ipsilateral peripheral projections, and both arborize mostly in the hemiganglion where they reside. Thus, we conclude that peripheral regulation of central neurogenesis is mediated in the leech by inductive signals conveyed retrogradely to each hemiganglion by specific central neurons that innervate this target and the hemiganglion they affect.
Hoxb-13: a new Hox gene in a distant region of the HOXB cluster maintains colinearity
Authors: Zeltser Lori , Desplan Claude , Heintz Nathaniel 
Published: April 2021

ABSTRACT
The Hox genes are involved in patterning along the A/P axes of animals. The clustered organization of Hox genes is conserved from nematodes to vertebrates. During evolution, the number of Hox genes within the ancestral complex increased, exemplified by the five-fold amplification of the AbdB-related genes, leading to a total number of thirteen paralogs. This was followed by successive duplications of the cluster to give rise to the four vertebrate HOX clusters. A specific subset of paralogs was subsequently lost from each cluster, yet the composition of each cluster was likely conserved during tetrapod evolution. While the HOXA, HOXC and HOXD clusters contain four to five AbdB-related genes, only one gene (Hoxb-9) is found in the HOXB complex. We have identified a new member of paralog group 13 in human and mouse, and shown that it is in fact Hoxb-13. A combination of genetic and physical mapping demonstrates that the new gene is found approx. 70 kb upstream of Hoxb-9 in the same transcriptional orientation as the rest of the cluster. Despite its relatively large distance from the HOX complex, Hoxb-13 exhibits temporal and spatial colinearity in the main body axis of the mouse embryo. The onset of transcription occurs at E9.0 in the tailbud region. At later stages of development, Hoxb-13 is expressed in the tailbud and posterior domains in the spinal cord, digestive tract and urogenital system. However, it is not expressed in the secondary axes such as the limbs and genital tubercle. These results indicate that the 5′ end of the HOXB cluster has not been lost and that at least one member exists and is highly conserved among different vertebrate species. Because of its separation from the complex, Hoxb-13 may provide an important system to dissect the mechanism(s) responsible for the maintenance of colinearity.
Transient release of calcium from inositol 1,4,5-trisphosphate-specific stores regulates mouse preimplantation development
Authors: Stachecki James J. , Armant D. Randall 
Published: April 2021

ABSTRACT
Inositol 1,4,5-trisphosphate can regulate growth and differentiation by modulating the release of intracellular Ca2+ in a variety of cellular systems, and it is involved in oocyte activation. Recent studies suggest that mammalian preimplantation development may also be regulated by the release of Ca2+ from intracellular stores. The rate of cavitation and cell division was accelerated after a transient elevation of intracellular Ca2+ levels was induced in morulae by exposure to ethanol or ionomycin. Embryos exposed to BAPTA-AM, a chelator of intracellular Ca2+, exhibited a brief dose-dependent reduction in basal Ca2+ levels, a temporal inhibition of ionophore-induced Ca2+ signalling and a subsequent delay in blastocoel formation. BAPTA-AM at 0.5 μM did not significantly alter the basal intracellular calcium level, but chelated Ca2+ that was released after ethanol exposure and thereby attenuated the ethanol-induced acceleration of cavitation. BAPTA-AM also inhibited cell division to the 16-cell stage in a dosedependent manner, which correlated with the inhibition of cavitation. Thimerosal and inositol 1,4,5-trisphosphate significantly elevated the intracellular Ca2+ concentration in mouse morula-stage embryos, providing evidence for the existence of inositol 1,4,5-trisphosphate-sensitive Ca2+ stores. Although caffeine failed to release intracellular Ca2+, ryanodine induced a small biphasic release of Ca2+, suggesting that ryanodine-sensitive Ca2+ stores may also exist in mouse embryos. Morulae exposed to the calmodulin inhibitor W-7 exhibited a dose-dependent delay in blastocoel formation. A 4 hour exposure to 10 μM W-7 did not significantly alter cavitation, but attenuated the ionophore-induced stimulation of blastocoel formation. This finding suggests that the developmental effects produced through Ca2+ signalling are mediated by calmodulin. Our results demonstrate that Ca2+ release in mouse morulae occurs predominantly through the inositol 1,4,5trisphosphate receptor, and that alteration of intracellular Ca2+ levels can accelerate or delay embryonic growth and differentiation, providing a mechanistic link between the regulation of oocyte and embryonic development.
Insulin-like growth factor-I stimulates neurogenesis in chick retina by regulating expression of the α6 integrin subunit
Authors: M. Frade José , Martí Elisa , Bovolenta Paola , Ángeles Rodríguez-Peña M. , Pérez-García David , Rohrer Hermann , Edgar David , Rodríguez-Tébar Alfredo 
Published: April 2021

ABSTRACT
Insulin-like growth factor I (IGF-I) strongly stimulates the generation of differentiated neurons in cultures of neuroepithelial cells of the embryonic chick neural retina in the presence of a laminin-1 tissue culture substrate. Treatment of cultured neuroepithelial cells with IGF-I rapidly up-regulated the mRNA coding for the α6 integrin subunit whereas specific reduction of α6 subunit levels by treatment with an α6 integrin antisense oligonucleotide resulted in reduced neuronal differentiation in vitro. Although IGF-I immunoreactivity is seen throughout the neural retina, expression of IGF-I mRNA is confined to the pigment epithelium during the period of neurogenesis in vivo. Neutralization of the endogenous IGF-I with a blocking antibody down-regulated levels of α6 integrin mRNA and reduced the production of differentiated retinal neurons in vivo. These data indicate a role for IGF-I in the generation of retinal neurons mediated by the interaction of laminin with its α6 integrin subunit-containing receptor.
Mutations affecting neurogenesis and brain morphology in the zebrafish, Danio rerio
Authors: Jiang Yun-Jin , Brand Michael , Heisenberg Carl-Philipp , Beuchle Dirk , Furutani-Seiki Makoto , Kelsh Robert N. , Warga Rachel M. , Granato Michael , Haffter Pascal , Hammerschmidt Matthias , Kane Donald A. , Mullins Mary C. , Odenthal Jörg , Eeden Fredericus J. M. van , Nüsslein-Volhard Christiane 
Published: April 2021

ABSTRACT
In a screen for embryonic mutants in the zebrafish a large number of mutants were isolated with abnormal brain morphology. We describe here 26 mutants in 13 complementation groups that show abnormal development of large regions of the brain. Early neurogenesis is affected in white tail (wit). During segmentation stages, homozygous wit embryos display an irregularly formed neural keel, particularly in the hindbrain. Using a variety of molecular markers, a severe increase in the number of various early differentiating neurons can be demonstrated. In contrast, late differentiating neurons, radial glial cells and some non-neural cell types, such as the neural crest-derived melanoblasts, are much reduced. Somitogenesis appears delayed. In addition, very reduced numbers of melanophores are present posterior to the mid-trunk. The wit phenotype is reminiscent of neurogenic mutants in Drosophila, such as Notch or Delta. In mutant parachute (pac) embryos the general organization of the hindbrain is disturbed and many rounded cells accumulate loosely in the hindbrain and midbrain ventricles. Mutants in a group of 6 genes, snakehead(snk), natter (nat), otter (ott), fullbrain (ful), viper (vip) and white snake (wis) develop collapsed brain ventricles, before showing signs of general degeneration. atlantis (atl), big head (bid), wicked brain (win), scabland (sbd) and eisspalte (ele) mutants have different malformation of the brain folds. Some of them have transient pheno-types, and mutant individuals may grow up to adults.
Mutations affecting the cardiovascular system and other internal organs in zebrafish
Authors: Chen Jau-Nian , Haffter Pascal , Odenthal Jörg , Vogelsang Elisabeth , Brand Michael , Eeden Fredericus J. M. van , Furutani-Seiki Makoto , Granato Michael , Hammerschmidt Matthias , Heisenberg Carl-Philipp , Jiang Yun-Jin , Kane Donald A. , Kelsh Robert N. , Mullins Mary C. , Nüsslein-Volhard Christiane 
Published: April 2021

ABSTRACT
In a screen for early developmental mutants of the zebrafish, we have identified mutations specifically affecting the internal organs. We identified 53 mutations affecting the cardiovascular system. Nine of them affect specific landmarks of heart morphogenesis. Mutations in four genes cause a failure in the fusion of the bilateral heart primordia, resulting in cardia bifida. In lonely atrium, no heart venticle is visible and the atrium is directly fused to the outflow tract. In the overlooped mutant, the relative position of the two heart chambers is distorted. The heart is enormously enlarged in the santa mutant. In two mutants, scotch tape and superglue, the cardiac jelly between the two layers of the heart is significantly reduced. We also identified a number of mutations affecting the function of the heart. The mutations affecting heart function can be subdivided into two groups, one affecting heart contraction and another affecting the rhythm of the heart beat. Among the contractility group of mutants are 5 with no heart beat at all and 15 with a reduced heart beat of one or both chambers. 6 mutations are in the rhythmicity group and specifically affect the beating pattern of the heart. Mutations in two genes, bypass and kurzschluss, cause specific defects in the circulatory system. In addition to the heart mutants, we identified 23 mutations affecting the integrity of the liver, the intestine or the kidney. In this report, we demonstrate that it is feasible to screen for genes specific for the patterning or function of certain internal organs in the zebrafish. The mutations presented here could serve as an entrypoint to the establishment of a genetic hierarchy underlying organogenesis.
A flipbook of zebrafish embryogenesis
Authors: Karlstrom Rolf O. , Kane Donald A. 
Published: April 2021

ABSTRACT
We modified a time-lapse recording to make a ‘flipbook’ of zebrafish embryogenesis. By flipping through the pages of this issue and watching the pictures in the upper corner of each even-numbered page, the dynamic cellular movements that form the zebrafish embryo can be visualized. The time-lapse record starts at the 2-cell stage (page 2 and Fig. 1B) and ends at the 16-somite stage (Fig. 1I), approximately 17 hours later.