bluuebunny/crossref_metadata_2025_split huggingface dataset:
The control of rostrocaudal pattern in the developing spinal cord: specification of motor neuron subtype identity is initiated by signals from paraxial mesoderm
Authors: Ensini Monica , Tsuchida Tammy N. , Belting Heinz-Georg , Jessell Thomas M. 
Published: April 2021

ABSTRACT
The generation of distinct classes of motor neurons is an early step in the control of vertebrate motor behavior. To study the interactions that control the generation of motor neuron subclasses in the developing avian spinal cord we performed in vivo grafting studies in which either the neural tube or flanking mesoderm were displaced between thoracic and brachial levels. The positional identity of neural tube cells and motor neuron subtype identity was assessed by Hox and LIM homeodomain protein expression. Our results show that the rostrocaudal identity of neural cells is plastic at the time of neural tube closure and is sensitive to positionally restricted signals from the paraxial mesoderm. Such paraxial mesodermal signals appear to control the rostrocaudal identity of neural tube cells and the columnar subtype identity of motor neurons. These results suggest that the generation of motor neuron subtypes in the developing spinal cord involves the integration of distinct rostrocaudal and dorsoventral patterning signals that derive, respectively, from paraxial and axial mesodermal cell groups.
Symplasmic fields in the tunica of the shoot apical meristem coordinate morphogenetic events
Authors: Rinne Päivi L. H. , Schoot Christiaan van der 
Published: April 2021

ABSTRACT
In plants, complex cellular interactions, which require the exchange of morphogenetic signals, underlie morphogenesis at the shoot apical meristem. Since all apical meristem cells are interconnected by plasmodesmata, we have investigated if symplasmic paths are available which may preferentially channel metabolites and potential morphogens in the apical meristem, and whether they could support both the formation of determinate appendages and the sustainment of an undifferentiated centre. Experiments in which the permeability of the symplasm was probed with fluorescent dye revealed that the tunica of the apical meristem of birch seedlings (Betula pubescence Ehrh.) is symplasmically compartmentalized into two concentric fields, which restrict the symplasmic diffusion of small potential morphogens to the cells inside their boundaries. A transient connection between the two fields was established early in a plastochron, potentiating the radial exchange of symplasmically diffusing signalling molecules. We suggest that the symplasmic subdivision of the tunica offers a means to unite cells into communication compartments, invoke boundary interactions between them, and shield the distal meristem cells from organogenesis. Electrophysiological measurements indicate that, in addition, the cells of these fields constitute metabolic working units. The relevance of these symplasmic fields for morphogenesis was established experimentally by treatment with short photoperiod, which induced breakdown of the fields into symplasmically isolated cells. Tannic acid staining and in situ immunolocalisation revealed that cell isolation was due to the activation of glucan synthase complexes intrinsic to sphincters. As a result callose plugs were formed on all plasmodesmata leading to morphogenetic deactivation.
A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF
Authors: Benjamin Laura E. , Hemo Itzhak , Keshet Eli 
Published: April 2021

ABSTRACT
Little is known about how the initial endothelial plexus is remodelled into a mature and functioning vascular network. Studying postnatal remodelling of the retina vasculature, we show that a critical step in vascular maturation, namely pericyte recruitment, proceeds by outmigration of cells positive for α-smooth muscle actin from arterioles and that coverage of primary and smaller branches lags many days behind formation of the endothelial plexus. The transient existence of a pericyte-free endothelial plexus coincides temporally and spatially with the process of hyperoxia-induced vascular pruning, which is a mechanism for fine tuning of vascular density according to available oxygen. Acquisition of a pericyte coating marks the end of this plasticity window.
To substantiate that association with pericytes stabilizes the vasculature, endothelial-pericyte associations were disrupted by intraocular injection of PDGF-BB. Ectopic PDGF-BB caused the detachment of PDGF-β receptor-positive pericytes from newly coated vessels, presumably through interference with endogenous cues, but had no effect on mature vessels. Disruption of endothelial-pericyte associations resulted in excessive regression of vascular loops and abnormal remodelling. Conversely, intraocular injection of VEGF accelerated pericyte coverage of the preformed endothelial plexus, thereby revealing a novel function of this pleiotropic angiogenic growth factor. These findings also provide a cellular basis for clinical observations that vascular regression in premature neonates subjected to oxygen therapy [i.e. in retinopathy of prematurity] drops precipitously upon maturation of retina vessels and a mechanistic explanation to our previous findings that VEGF can rescue immature vessels from hyperoxia-induced regression.
Adenovirus-mediated ectopic expression of Msx2 in even-numbered rhombomeres induces apoptotic elimination of cranial neural crest cells in ovo
Authors: Takahashi Katsu , Nuckolls Glen H. , Tanaka Osamu , Semba Ichiro , Takahashi Ichiro , Dashner Ralph , Shum Lillian , Slavkin Harold C. 
Published: April 2021

ABSTRACT
Distinct cranial neural crest-derived cell types (a number of neuronal as well as non-neuronal cell lineages) are generated at characteristic times and positions in the rhombomeres of the hindbrain in developing vertebrate embryos. To examine this developmental process, we developed a novel strategy designed to test the efficacy of gain-of-function Msx2 expression within rhombomeres in ovo prior to the emigration of cranial neural crest cells (CNCC). Previous studies indicate that CNCC from odd-numbered rhombomeres (r3 and r5) undergo apoptosis in response to exogenous BMP4. We provide evidence that targeted infection in ovo using adenovirus containing Msx2 and a reporter molecule indicative of translation can induce apoptosis in either even- or odd-numbered rhombomeres. Furthermore, infected lacZ-control explants indicated that CNCC emigrated, and that 20% of these cells were double positive for crest cell markers HNK-1 and β-gal. In contrast, there were no HNK-1 and Msx2 double positive cells emigrating from Msx2 infected explants. These results support the hypothesis that apoptotic elimination of CNCC can be induced by ‘gain-of-function’ Msx2 expression in even-numbered rhombomeres. These inductive interactions involve qualitative, quantitative, positional and temporal differences in TGF-β-related signals, Msx2 expression and other transcriptional control.
Murine Otx1 and Drosophila otd genes share conserved genetic functions required in invertebrate and vertebrate brain development
Authors: Acampora Dario , Avantaggiato Virginia , Tuorto Francesca , Barone Paolo , Reichert Heinrich , Finkelstein Robert , Simeone Antonio 
Published: April 2021

ABSTRACT
Despite the obvious differences in anatomy between invertebrate and vertebrate brains, several genes involved in the development of both brain types belong to the same family and share similarities in expression patterns. Drosophila orthodenticle (otd) and murine Otx genes exemplify this, both in terms of expression patterns and mutant phenotypes. In contrast, sequence comparison of OTD and OTX gene products indicates that homology is restricted to the homeodomain suggesting that protein divergence outside the homeodomain might account for functional differences acquired during brain evolution. In order to gain insight into this possibility, we replaced the murine Otx1 gene with a Drosophila otd cDNA. Strikingly, epilepsy and corticogenesis defects due to the absence of Otx1 were fully rescued in homozygous otd mice. A partial rescue was also observed for the impairments of mesencephalon, eye and lachrymal gland. In contrast, defects of the inner ear were not improved suggesting a vertebrate Otx1-specific function involved in morphogenesis of this structure. Furthermore, otd, like Otx1, was able to cooperate genetically with Otx2 in brain patterning, although with reduced efficiency. These data favour an extended functional conservation between Drosophila otd and murine Otx1 genes and support the idea that conserved genetic functions required in mammalian brain development evolved in a primitive ancestor of both flies and mice.
Wnt and TGFβ signals subdivide the AbdA Hox domain during Drosophila mesoderm patterning
Authors: Bilder David , Graba Yacine , Scott Matthew P. 
Published: April 2021

ABSTRACT
Hox genes have large expression domains yet control the formation of fine pattern elements at specific locations. We have examined the mechanism underlying subdivision of the abdominal-A (abdA) Hox domain in the visceral mesoderm. AbdA directs formation of an embryonic midgut constriction at a precise location within the broad and uniform abdA expression domain. The constriction divides the abdA domain of the midgut into two chambers, the anterior one producing the Pointed (Pnt) ETS transcription factors and the posterior one the Odd-paired (Opa) zinc finger protein. Transcription of both pnt and opa is activated by abdA but the adjacent non-overlapping patterns are not due to mutual opa-pnt regulation. Near the anterior limit of the abdA domain, two signals, Dpp (a TGFβ ) and Wg (a Wnt), are produced, in adjacent non-overlapping patterns, under Hox control in mesoderm cells. The two signals are known to regulate local mesodermal cell fates and to signal to the endoderm. We find that, in addition, they precisely subdivide the abdA domain: Wg acts upon anterior abdA domain cells to activate pnt transcription, while Dpp is essential in the same region to prevent abdA from activating opa transcription. pnt activation is required to determine the appropriate numbers of mesodermal cells in the third midgut chamber.
Spatial response to fibroblast growth factor signalling inXenopusembryos
Authors: Christen B. , Slack J. M. W. 
Published: April 2021

AbstractWe have examined the spatial pattern of activation of the extracellular signal-regulated protein kinase (ERK) during Xenopus development, and show that it closely resembles the expression of various fibroblast growth factors (FGFs). Until the tailbud stage of development, all ERK activation domains are sensitive to the dominant negative FGF receptor, showing that activation is generated by endogenous FGF signalling. ERK is not activated by application of other growth factors like BMP4 or activin, nor is endogenous activation blocked by the respective dominant negative receptors. This shows that various domains of FGF expression, including the periblastoporal region and the midbrain-hindbrain boundary, are also sites of FGF signalling in vivo.Wounding induces a transient (&lt;60 minutes) activation of ERK which is not significantly reduced by the dominant negative FGF receptor.An artificial FGF source, created by injection of eFGF mRNA into cleavage stage embryos, provokes ERK activation outside of its injection site over a range of several cell diameters. The range and extent of ERK activation outside the source region is unchanged by co-injection of a dominant negative form of Ras, which blocks ERK-activation within the source. This suggests that FGF protein can diffuse over several cell diameters.
COG-2, a Sox domain protein necessary for establishing a functional vulval- uterine connection in Caenorhabditis elegans
Authors: Hanna-Rose Wendy , Han Min 
Published: April 2021

ABSTRACT
In screens for mutants defective in vulval morphogenesis, multiple mutants were isolated in which the uterus and the vulva fail to make a proper connection. We describe five alleles that define the gene cog-2, forconnection of gonad defective. To form a functional connection between the vulva and the uterus, the anchor cell must fuse with the multinucleate uterine seam cell, derived from uterine cells that adopt a π lineage. In cog-2mutants, the anchor cell does not fuse to the uterine seam cell and, instead, remains at the apex of the vulva, blocking the connection between the vulval and uterine lumens, resulting in an egg-laying defective phenotype. According to lineage analysis and expression assays for two π-cell-specific markers, induction of the πfate occurs normally in cog-2mutants. We have cloned cog-2and shown that it encodes a Sox family transcription factor that is expressed in the π lineage. Thus, it appears that COG-2 is a transcription factor that regulates a late-stage aspect of uterine seam cell differentiation that specifically affects anchor cell-uterine seam cell fusion.
In vivo analysis using variants of zebrafish BMPR-IA: range of action and involvement of BMP in ectoderm patterning
Authors: Nikaido Masataka , Tada Masazumi , Takeda Hiroyuki , Kuroiwa Atsushi , Ueno Naoto 
Published: April 2021

ABSTRACT
It has been an intriguing problem whether the polypeptide growth factors belonging to the transforming growth factor-β (TGF-β) superfamily function as direct and long- range signaling molecules in pattern formation of the early embryo. In this study, we examined the mechanism of signal propagation of bone morphogenetic protein (BMP) in the ectodermal patterning of zebrafish embryos, in which BMP functions as an epidermal inducer and a neural inhibitor. To estimate the effective range ofzbmp-2, we first performed whole-mount in situ hybridization analysis. The zbmp-2-expressing domain and the neuroectoderm, marked by otx-2 expression, were complementary, suggesting that BMP has a short-range effect in vivo. Moreover, mosaic experiments using a constitutively active form of a zebrafish BMP type I receptor (CA-BRIA) demonstrated that the cell-fate conversion, revealed by ectopic expression of gata-3 and repression of otx-2, occurred in a cell- autonomous manner, denying the involvement of the relay mechanism. We also found that zbmp-2 was induced cell autonomously within the transplanted cells in the host ectoderm, suggesting that BMP cannot influence even the neighboring cells. This result is consistent with the observation that there is no gap between the expression domains of zbmp-2 and otx-2. Taken together, we propose that, in ectodermal patterning, BMP exerts a direct and cell-autonomous effect to fate uncommitted ectodermal cells to become epidermis.
F-actin marks the rhizoid pole in living Pelvetia compressa zygotes
Authors: Alessa Lilian , Kropf Darryl L. 
Published: April 2021

ABSTRACT
Spatial and temporal changes in F-actin during polarity establishment in Pelvetia compressa zygotes were investigated using vital staining with rhodamine phalloidin (RP). F-actin was localized to a patch in the cortex of young zygotes. When unilateral light was applied to induce a growth axis (photopolarization) in a population of zygotes, the cortical F-actin patches localized at the shaded pole (rhizoid pole of growth axis). Treatments that prevented photopolarization prevented localization of F-actin patches to the shaded pole. When the direction of the light treatment was reversed, the previous growth axis was abandoned and a new axis was established in the opposite direction. The F-actin patch repositioned to the new rhizoid pole within minutes of light reversal, indicating that F-actin was an immediate marker of the nascent growth axis. Repositioning probably occurred by disassembly of the initial patch and reassembly of a new one. The patch grew in size as zygotes developed, eventually becoming a ring just prior to rhizoid outgrowth. The rhizoid emerged at the site of the F-actin ring and, following germination, the ring was located in the subapical zone of the elongating tip.
The DAF-3 Smad binds DNA and represses gene expression in the Caenorhabditis elegans pharynx
Authors: Thatcher Jack D. , Okkema Christina Haun , Okkema Peter G. 
Published: April 2021

ABSTRACT
Gene expression in the pharyngeal muscles of Caenorhabditis elegans is controlled in part by organ-specific signals, which in the myo-2 gene target a short DNA sequence termed the C subelement. To identify genes contributing to these signals, we performed a yeast one-hybrid screen for cDNAs encoding factors that bind the C subelement. One clone recovered was from daf-3, which encodes a Smad most closely related to vertebrate Smad4. We demonstrated that DAF-3 binds C subelement DNA directly and specifically using gel mobility shift and DNase1 protection assays. Mutation of any base in the sequence GTCTG interfered with binding in the gel mobility shift assay, demonstrating that this pentanucleotide is a core recognition sequence for DAF-3 binding. daf-3 is known to promote formation of dauer larvae and this activity is negatively regulated by TGFβ-like signaling. To determine how daf-3 affects C subelement enhancer activity in vivo, we examined expression a gfp reporter controlled by a concatenated C subelement oligonucleotide in daf-3 mutants and other mutants affecting the TGFβ-like signaling pathway controlling dauer formation. Our results demonstrate that wild-type daf-3 can repress C subelement enhancer activity during larval development and, like its dauer-promoting activity, daf-3’s repressor activity is negatively regulated by TGFβ-like signaling. We have examined expression of this gfp reporter in dauer larvae and have observed no daf-3-dependent repression of C activity. These results suggest daf-3 directly regulates pharyngeal gene expression during non-dauer development.
Dual role for Hedgehog in the regulation of the proneural gene atonal during ommatidia development
Authors: Domínguez María 
Published: April 2021

ABSTRACT
The differentiation of cells in the Drosophila eye is precisely coordinated in time and space. Each ommatidium is founded by a photoreceptor (R)8 cell and these founder cells are added in consecutive rows. Within a row, the nascent R8 cells appear in precise locations that lie out of register with the R8 cells in the previous row. The bHLH protein Atonal determines the development of the R8 cells. The expression of atonal is induced shortly before the selection of a new row of R8 cells and is initially detected in a stripe. Subsequently atonal expression resolves into regularly spaced clusters (proneural clusters) that prefigure the positions of the future R8 cells. The serial induction of atonal expression, and hence the increase in the number of rows of R8 cells, requires Hedgehog function. Here it is shown that, in addition to this role, Hedgehog signalling is also required to repress atonal expression between the nascent proneural clusters. This repression has not been previously described and appears to be critical for the positioning of Atonal proneural clusters and, therefore, the R8 cells. The two temporal responses to Hedgehog are due to direct stimulation of the responding cells by Hedgehog itself.
The Caenorhabditis elegans genes egl-27 and egr-1 are similar to MTA1, a member of a chromatin regulatory complex, and are redundantly required for embryonic patterning
Authors: Solari Florence , Bateman Alex , Ahringer Julie 
Published: April 2021

ABSTRACT
We show here that two functionally redundant Caenorhabditis elegans genes, egl-27 and egr-1, have a fundamental role in embryonic patterning. When both are inactivated, cells in essentially all regions of the embryo fail to be properly organised. Tissue determination and differentiation are unaffected and many zygotic patterning genes are expressed normally, including HOX genes. However, hlh-8, a target of the HOX gene mab-5, is not expressed. egl-27 and egr-1 are members of a gene family that includes MTA1, a human gene with elevated expression in metastatic carcinomas. MTA1 is a component of a protein complex with histone deacetylase and nucleosome remodelling activities. We propose that EGL-27 and EGR-1 function as part of a chromatin regulatory complex required for the function of regional patterning genes.
Retinoic acid is required in the mouse embryo for left-right asymmetry determination and heart morphogenesis
Authors: Chazaud Claire , Chambon Pierre , Dollé Pascal 
Published: April 2021

ABSTRACTDetermination of the left-right position (situs) of visceral organs involves lefty, nodal and Pitx2 genes that are specifically expressed on the left side of the embryo. We demonstrate that the expression of these genes is prevented by the addition of a retinoic acid receptor pan-antagonist to cultured headfold stage mouse embryos, whereas addition of excess retinoic acid leads to their symmetrical expression. Interestingly, both treatments lead to randomization of heart looping and to defects in heart anteroposterior patterning. A time course analysis indicates that only the newly formed mesoderm at the headfold-presomite stage is competent for these retinoid effects. We conclude that retinoic acid, the active derivative of vitamin A, is essential for heart situs determination and morphogenesis.
The mammalian Tolloid-like 1 gene, Tll1, is necessary for normal septation and positioning of the heart
Authors: Clark Timothy G. , Conway Simon J. , Scott Ian C. , Labosky Patricia A. , Winnier Glenn , Bundy Justin , Hogan Brigid L. M. , Greenspan Daniel S. 
Published: April 2021

ABSTRACT
Mammalian Tolloid-like 1 (mTLL-1) is an astacin-like metalloprotease, highly similar in domain structure to the morphogenetically important proteases bone morphogenetic protein-1 (BMP-1) and Drosophila Tolloid. To investigate possible roles for mTLL-1 in mammalian development, we have used gene targeting in ES cells to produce mice with a disrupted allele for the corresponding gene, Tll1. Homozygous mutants were embryonic lethal, with death at mid-gestation from cardiac failure and a unique constellation of developmental defects that were apparently confined solely to the heart. Constant features were incomplete formation of the muscular interventricular septum and an abnormal and novel positioning of the heart and aorta. Consistent with roles in cardiac development, Tll1 expression was specific to precardiac tissue and endocardium in 7.5 and 8.5 days p.c.embryos, respectively. Tll1 expression was also high in the developing interventricular septum, where expression of the BMP-1 gene, Bmp1, was not observed. Cardiac structures that were not affected in Tll1−/− embryos either showed no Tll1 expression (atrio-ventricular cushions) or showed overlapping expression of Tll1 and Bmp1 (aortico-pulmonary septum), suggesting that products of the Bmp1 gene may be capable of functionally substituting for mTLL-1 at sites in which they are co-expressed. Together, the various data show that mTLL-1 plays multiple roles in formation of the mammalian heart and is essential for formation of the interventricular septum.