bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonradial migration of interneurons can be experimentally altered in spinal cord slice cultures
Authors: Phelps Patricia E. , Barber Robert P. , Vaughn James E. 
Published: April 2021

ABSTRACT
During development, many migrating neurons are thought to guide on radially oriented glia to reach their adult locations. However, members of the ‘U-shaped’ group of cholinergic interneurons in embryonic rat spinal cord appeared to migrate in a direction perpendicular to the orientation of radial glia. This ‘U-shaped’ group of cells was located around the ventral ventricular zone on embryonic day 16 and, during the next two days, the constituent cells dispersed into the dorsal horn or around the central canal. During this period, these cells could be identified with either ChAT immunocytochemistry or NADPHdiaphorase histochemistry and they appeared to be aligned along commissural axons, suggesting that such processes, rather than radial glia, might guide their migration.
An organotypic spinal cord slice preparation was developed and utilized for three different experimental approaches to studying this migration. In the first experiments, slices of embryonic day 16 cervical spinal cord were cultured for one, two or three days, and a relatively histotypic dorsal migration of ‘U-derived’ cells could be inferred from these sequential cultures. A second set of experiments focused on the direct observation of dorsally directed migration in living spinal cord cultures. Embryonic day 16 slices were injected with a lipophilic fluorescent label near the dorsal boundary of the ‘U-shaped’ cell group and the dorsal movement of labeled cells was observed using confocal microscopy. These experiments confirmed the dorsal migratory pattern inferred from sequentially fixed specimens. A third experimental approach was to transect embryonic day 16 slice cultures microsurgically in order to disturb the migration of ‘U-derived’ cells. Depending upon the amount of ventral spinal cord removed, the source of cells was excised and/or their guidance pathway was perturbed. The number and position of ‘U-derived’ cells varied with the amount of ventral cord excised. If more than 400 μm was removed, no ‘U-derived’ diaphoraselabeled cells were present, whereas if only 200-300 μm was removed, the cultures contained such cells. However, in this instance, many of the ‘U-derived’ neurons did not move as far dorsally, nor did they display their characteristic dorsoventral orientation. When results from these three experiments are taken together, they provide strong evidence that nonradial neuronal migration occurs in developing spinal cord and that the ‘U-derived’ neurons utilize such a migration to move from their ventral generation sites to their dorsal adult locations.
Expression domains of a zebrafish homologue of the Drosophila pair-rule gene hairy correspond to primordia of alternating somites
Authors: Müller Marcus , Weizsäcker Elisabeth v. , Campos-Ortega José A. 
Published: April 2021

ABSTRACT
her1 is a zebrafish cDNA encoding a bHLH protein with all features characteristic of members of the Drosophila HAIRY-E(SPL) family. During late gastrulation stages, her1 is expressed in the epibolic margin and in two distinct transverse bands of hypoblastic cells behind the epibolic front. After completion of epiboly, this pattern persists essentially unchanged through postgastrulation stages; the marginal domain is incorporated in the tail bud and, depending on the time point, either two or three paired bands of expressing cells are present within the paraxial presomitic mesoderm separated by regions devoid of transcripts. Labelling of cells within the her1 expression domains with fluorescein-dextran shows that the cells in the epibolic margin and the tail bud are not allocated to particular somites. However, allocation of cells to somites occurs between the marginal expression domain and the first expression band, anterior to it. Moreover, the her1 bands, and the intervening non-expressing zones, each represents the primordium of a somite. This expression pattern is highly reminiscent of that of Drosophila pair-rule genes. A possible participation of her1 in functions related to somite formation is discussed.
Involvement of bone morphogenetic protein-4 and bone morphogenetic protein-7 in the differentiation of the adrenergic phenotype in developing sympathetic neurons
Authors: Reissmann E. , Ernsberger U. , Francis-West P. H. , Rueger D. , Brickell P. M. , Rohrer H. 
Published: April 2021

ABSTRACT
The neurotransmitter phenotype of sympathetic neurons is specified by interactions with the surrounding embryonic tissues. Adrenergic differentiation is elicited early during development in the vicinity of notochord and dorsal aorta and the importance of axial midline tissues for adrenergic differentiation has been well documented. We now provide evidence that bone morphogenetic proteins, BMP-4 and BMP-7 are signals produced by the dorsal aorta that direct sympathetic neuron differentiation. BMP-4 and BMP-7 are expressed in the dorsal aorta at critical times during sympathetic neuron differentiation and have the ability to enhance the formation of adrenergic sympathetic neurons both in cultures of neural crest cells and when ectopically expressed in the developing embryo.
Profilin is required for posterior patterning of the Drosophila oocyte
Authors: Manseau Lynn , Calley John , Phan Huy 
Published: April 2021

ABSTRACT
We have investigated the role of the actin cytoskeleton during mid-oogenesis and have found that disrupting the actin cytoskeleton with cytochalasin D induces microtubule bundling and microtubule-based cytoplasmic streaming within the oocyte, similar to that which occurs prematurely in cappuccino and spire mutant oocytes. After examining a number of mutants that affect the actin cytoskeleton, we have found that chickadee, which encodes the actin-binding protein, profilin, shares this phenotype. In addition to the microtubule misregulation, mutants in chickadee resemble cappuccino in that they fail to localize STAUFEN and oskar mRNA to the posterior pole of the developing oocyte. Also, a strong allele of cappuccino has multinucleate nurse cells, similar to those previously described in chickadee. In an independent line of experiments, we have identified profilin as a CAPPUCCINO interactor in a two-hybrid screen for proteins that bind to CAPPUCCINO. This, together with the similarity of mutant phenotypes, suggests that profilin and CAPPUCCINO may interact during development.
Symmetry breakage in the development of one-armed gonads in nematodes
Authors: Félix Marie-Anne , Sternberg Paul W. 
Published: April 2021

ABSTRACT
Whereas the hermaphrodite gonad of Caenorhabditis elegans has two symmetric arms (didelphy), the female/hermaphrodite gonad of many nematode species features a single anterior arm (monodelphy). We examined how gonadal cell lineages and intercellular signalling evolve to generate these diverse structures. In C. elegans, the two arms develop symmetrically from two somatic precursor cells, Z1 (anterior) and Z4 (posterior). Each first gives rise to one distal tip cell (which promotes arm growth and germ line proliferation), two ovary precursors and three uterine precursors in the center of the developing gonad. In monodelphic species, Z1 and Z4 have different fates. The first visible asymmetry between them is in the relative timing of their divisions, followed by asymmetric cell movements. The putative posterior distal tip cell is then eliminated in all but one species by programmed cell death. In some species the posterior ovary precursors form a small vestigial posterior arm, the post-vulval sac; in other species, they stay undivided, or die. In Cephalobus sp. PS1197, the specific fate of Z4 progeny is induced by Z1 (or its daughters). In the uterus in C. elegans, symmetric lateral signalling between Z1.ppp and Z4.aaa renders them equally likely to become the anchor cell, which links the uterus to the vulva. In the different monodelphic species, anchor cell specification is biased, or fully fixed, to a descendant of either Z1 or Z4. Replacement regulation upon anchor cell ablation is conserved in some species, but lost in others, leading to a mosaic-type development. Differentiation between Z1 and Z4 is thus manifested at this later stage in the breakage of symmetry of cell interactions in the ventral uterus.
Mad acts downstream of Dpp receptors, revealing a differential requirement for dpp signaling in initiation and propagation of morphogenesis in the Drosophila eye
Authors: Wiersdorff Volker , Lecuit Thomas , Cohen Stephen M. , Mlodzik Marek 
Published: April 2021

ABSTRACT
Decapentaplegic (Dpp), a member of the TGF-β family of cytokines, has been implicated in many patterning processes in Drosophila, including the initial steps of pattern formation in the developing eye. We show that the Mothers against dpp (Mad) gene is required for dpp signaling during eye development. Clonal analysis demonstrates a cell-autonomous function for Mad and genetic interactions indicate that Mad is an essential component of the signal transduction pathway downstream of the Dpp receptors in responding cells. Mad-mediated dpp signaling is absolutely required for the initiation of the morphogenetic furrow in the eye, but has only a minor role in its subsequent propagation across the eye disc. We also present evidence for the repression of wingless transcription by dpp signaling.
Expression of the met receptor tyrosine kinase in muscle progenitor cells in somites and limbs is absent in Splotch mice
Authors: Yang Xiu-Ming , Vogan Kyle , Gros Philippe , Park Morag 
Published: April 2021

ABSTRACT
Hepatocyte growth factor/scatter factor (HGF/SF) stimulates proliferation, dissociation, migration and morphogenesis of cells in culture. To investigate a possible role for HGF/SF and its receptor, the Met tyrosine kinase, in embryonic development, we have analyzed their expression in mouse embryos from day 7.5 of gestation by wholemount in situ hybridization. Met expression is first detected in the ventral portion of somites at day 9.25 of gestation (22 somite embryo) at the level of fore limb buds. As somites mature, met expression is detected in caudal somites, and is confined to the lateral and medial tips of the dermomyotome and dermomyotome/myotome respectively. In contrast, HGF/SF is expressed exclusively in the mesodermal core of the limb bud. As the dermomyotome elongates ventrolaterally, the met-expressing cells at the lateral tip appear to detach from the somite, invade the limb bud and localize at the dorsal and ventral limb sides in close proximity to HGF/SF-expressing cells. At later stages, both metand HGF/SF-expressing cells appear to migrate distally and localize to the digit forming area of the developing hand plate. Met expression in the lateral dermomyotome and limb bud coincides with expression of Pax-3, a marker for migrating muscle precursor cells in the somite and limb. Splotch-2H and Splotch-delayed mice, which harbor mutations in Pax-3, show major disruptions in early limb muscle development. Significantly, no met-expressing cells were observed in the limbs of homozygous Splotch-2H and Splotch-delayed animals, whereas HGF/SF expression was not affected. The restricted expression of met to a subpopulation of Pax-3-expressing cells in the lateral tip of the dermomyotome, demonstrates that met represents a unique molecular marker for this migratory cell population. From these observations, together with the biological activities of HGF/SF, we propose that in homozygous Splotch embryos the failure of muscle precursors to migrate into and populate the limb bud results from a loss of met expression in the cells at the ventrolateral edge of the somitic dermomyotome.
Redundant control of Ultrabithorax by zeste involves functional levels of zeste protein binding at the Ultrabithorax promoter
Authors: Laney Jeffrey D. , Biggin Mark D. 
Published: April 2021

ABSTRACT
Many biological processes appear to be controlled by functionally redundant genes or pathways, but it has proven difficult to understand the nature of this redundancy. Here, we have analyzed a redundant regulatory interaction between the Drosophila transcription factor zeste and the homeotic gene Ultrabithorax. Mutations in zeste do not affect the cis-regulation of the endogenous Ultrabithorax gene; however, the expression of small Ultrabithorax promoter constructs is strongly dependent upon zeste. We show that this difference is due to redundant cis-regulatory elements in the Ultrabithorax gene, which presumably contain binding sites for factors that share the function of zeste. We also provide evidence suggesting that zeste and the gene encoding the GAGA factor have an overlapping function in regulating Ultrabithorax. Furthermore, we show that the zeste protein is bound at equal levels in vivo to a Ultrabithorax promoter construct, which zeste strongly activates, and to the identical promoter region in the endogenous Ultrabithorax gene, which zeste redundantly regulates. These results suggest that zeste is significantly active in the wild-type animal and not simply a factor that is induced as a back-up when other activators fail.
Variation in the number of activated torso receptors correlates with differential gene expression
Authors: Furriols Marc , Sprenger Frank , Casanova Jordi 
Published: April 2021

ABSTRACT
Activation of receptor tyrosine kinases triggers many developmental decisions, yet we do not understand how activation of a single receptor can be transduced into different cell responses. The torso pathway in Drosophila provides a model to address this issue since it generates more than one response in the embryo. The torso receptor tyrosine kinase is activated at the embryonic poles under the control of trunk, a protein with similarities to several types of extracellular growth factors. Activation of torso is responsible for the development of a variety of structures, whose appearance can be correlated with activation of at least two different genes along the terminal region. In this study we have analyzed mutations in torso and trunk that express low levels of the respective proteins. We show that different amounts of torso or trunk molecules correlate with the expression of different zygotic genes, implicating changes in the number of activated torso molecules as one of the mechanisms defining differential gene expression. We suggest that variation in the number of activated receptors at the cell surface is a general mechanism that leads to differential gene expression and thus the generation of different cell responses.
Role of TGFβs and BMPs as signals controlling the position of the digits and the areas of interdigital cell death in the developing chick limb autopod
Authors: Gañan Y. , Macias D. , Duterque-Coquillaud M. , Ros M. A. , Hurle J. M. 
Published: April 2021

ABSTRACT
The establishment of the digital rays and the interdigital spaces in the developing limb autopod is accompanied by the occurrence of corresponding domains of expression of TGFβs and BMPs. This study analyzes whether these coincident events are functionally correlated. The experiments consisted of local administration of TGFβ-1, TGFβ-2 or BMP-4 by means of heparin or Affi-gel blue beads to the chick limb autopod in the stages preceding the onset of interdigital cell death. When beads bearing either TGFβ-1 or -2 were implanted in the interdigits, the mesodermal cells were diverted from the death program forming ectopic cartilages or extra digits in a doseand stagedependent fashion. This change in the interdigital phenotype was preceded by a precocious ectopic expression of ck-erg gene around the bead accompanied by down-regulation of bmp-4, msx-1 and msx-2 gene expression. When BMP-beads were implanted in the interdigital spaces, programmed cell death and the freeing of the digits were both accelerated. Implantation of beads bearing BMP-4 at the tip of the growing digits was followed by digit bifurcation, accompanied by the formation of an ectopic area of cell death resembling an extra interdigit, both morphologically and molecularly. The death-inducing effect of the BMP beads and the chondrogenic-inducing effect of the TGFβ beads were antagonized by the implantation of an additional bead preabsorbed with FGF-2, which constitutes a signal characteristic of the progress zone. It is concluded that the spatial distribution of digital rays and interdigital spaces might be controlled by a patterned distribution of TGFβs and BMPs in the mesoderm subjacent to the progress zone.
Xom: a Xenopus homeobox gene that mediates the early effects of BMP-4
Authors: Ladher R. , Mohun T. J. , Smith J. C. , Snape A. M. 
Published: April 2021

ABSTRACT
Bone morphogenetic protein-4 (BMP-4) is thought to play an important role in early Xenopus development by acting as a ‘ventralizing factor’ and as an epidermal determinant: local inhibition of BMP-4 function in whole embryos causes the formation of an additional dorsal axis, and inhibition of BMP-4 function in isolated ectodermal cells causes the formation of neural tissue. In this paper we describe a homeobox-containing gene whose expression pattern is similar to that of BMP-4, whose expression requires BMP-4 signalling and which, when over-expressed, causes a phenotype similar to that caused by over-expression of BMP-4. We suggest that this gene, which we call Xom, acts downstream of BMP-4 to mediate its effects.
The SM 22 promoter directs tissue-specific expression in arterial but not in venous or visceral smooth muscle cells in transgenic mice
Authors: Moessler H. , Mericskay M. , Li Z. , Nagl S. , Paulin D. , Small J. V. 
Published: April 2021

ABSTRACT
The transcriptional signals underlying smooth muscle differentiation are currently unknown. We report here the complete sequence and characterization of the single mouse gene for the smooth muscle-specific protein SM 22 and the transcriptional activity of its promoter in cultured smooth muscle cells in vitro and in transgenic mice. In the transgenic animals, promoter constructs ranging in length from 445 to 2126 bp directed reporter expression initially in the heart and the somites of embryos and subsequently in the arteries of the vascular system, but in none of the visceral muscles, nor in the veins. Expression in the heart was spatially restricted to the presumptive right ventricle and outflow tract and disappeared in the adult. Likewise, expression in the somites was only transitory and was not observed after about 14.5 days post coitum in the embryo. In the adult mouse, SM 22 promoter activity persisted in the smooth muscle cells of the arteries and was still notably absent from other smooth muscles, despite the ubiquitous presence of the endogenous SM 22 protein. These findings on the transcriptional activity of a smooth muscle promoter in vivo reveal the existence of different differentiation programmes for smooth muscle cells in the veins and the arteries and raise the expectation of a further subdivision of programmes among the visceral muscles.
Inhibition of Xbra transcription activation causes defects in mesodermal patterning and reveals autoregulation of Xbra in dorsal mesoderm
Authors: Conlon F. L. , Sedgwick S. G. , Weston K. M. , Smith J. C. 
Published: April 2021

ABSTRACT
The Brachyury (T) gene is required for formation of posterior mesoderm and for axial development in both mouse and zebrafish embryos. In this paper, we first show that the Xenopus homologue of Brachyury, Xbra, and the zebrafish homologue, no tail (ntl), both function as transcription activators. The activation domains of both proteins map to their carboxy terminal regions, and we note that the activation domain is absent in two zebrafish Brachyury mutations, suggesting that it is required for gene function. A dominant-interfering Xbra construct was generated by replacing the activation domain of Xbra with the repressor domain of the Drosophila engrailed protein. Microinjection of RNA encoding this fusion protein allowed us to generate Xenopus and zebrafish embryos which show striking similarities to genetic mutants in mouse and fish. These results indicate that the function of Brachyury during vertebrate gastrulation is to activate transcription of mesoderm-specific genes. Additional experiments show that Xbra transcription activation is required for regulation of Xbra itself in dorsal, but not ventral, mesoderm. The approach described in this paper, in which the DNA-binding domain of a transcription activator is fused to the engrailed repressor domain, should assist in the analysis of other Xenopus and zebrafish transcription factors.
The intracellular deletions of DELTA and SERRATE define dominant negative forms of the Drosophila Notch ligands
Authors: Sun Xin , Artavanis-Tsakonas Spyros 
Published: April 2021

ABSTRACT
We examined the function of the intracellular domains of the two known Drosophila Notch ligands, Delta and Serrate, by expressing wild-type and mutant forms in the developing Drosophila eye under the sevenless promoter. The expression of intracellularly truncated forms of either Delta (sev-DlTM) or Serrate (sev-SerTM) leads to extra photoreceptor phenotypes, similar to the eye phenotypes associated with loss-of-function mutations of either Notch or Delta. Consistent with the notion that the truncated ligands reduce Notch signalling activity, the eye phenotypes of sevDlTM and sev-SerTM are enhanced by loss-of-function mutations in the Notch pathway elements, Notch, Delta, mastermind, deltex and groucho, but are suppressed by a duplication of Delta or mutations in Hairless, a negative regulator of the pathway. These observations were extended to the molecular level by demonstrating that the expression of Enhancer of split mδ, a target of Notch signalling, is down-regulated by the truncated ligands highly expressed in neighbouring cells. We conclude that the truncated ligands act as antagonists of Notch signalling.
Inhibition of floor plate differentiation by Pax3: evidence from ectopic expression in transgenic mice
Authors: Tremblay Patrick , Pituello Fabienne , Gruss Peter 
Published: April 2021

ABSTRACT
The Pax genes containing a complete paired-type homeobox are expressed in restricted dorsoventral domains of the undifferentiated neuroepithelium. Their expression respond to signals that pattern the neural tube and which emanate from the notochord, floor plate and overlying ectoderm. In order to determine whether the dorsally restricted Pax3 gene can influence the fate of cells within the neural tube, we produced transgenic mice overexpressing Pax3 in the entire neural tube under the Hoxb4 promoter/region A enhancer. In two distinct transgenic mouse lines, we observed embryos with abnormal limb, eye, brain and neural tube development. Expression of Pax3 was not sufficient to dorsalize cells from the ventral intermediate zone, which still expressed ventral markers. However, in these embryos, expression of Pax3 at the ventral midline was associated with the absence of floor plate differentiation. Under these conditions, motor neurons still differentiated in the ventral spinal cord, although in fewer numbers.