bluuebunny/crossref_metadata_2025_split huggingface dataset:
The zebrafish gene cloche acts upstream of a flk-1 homologue to regulate endothelial cell differentiation
Authors: Liao Wayne , Bisgrove Brent W. , Sawyer Holly , Hug Barbara , Bell Bridgit , Peters Kevin , Grunwald David J. , Stainier Didier Y. R. 
Published: April 2021

ABSTRACT
The zebrafish cloche mutation affects both the endothelial and hematopoietic lineages at a very early stage (Stainier, D. Y. R., Weinstein, B. M., Detrich, H. W., Zon, L. I. and Fishman, M. C. (1995). Development 121, 3141-3150). The most striking vascular phenotype is the absence of endocardial cells from the heart. Microscopic examination of mutant embryos reveals the presence of endothelial-like cells in the lower trunk and tail regions while head vessels appear to be missing, indicating a molecular diversification of the endothelial lineage. Cell transplantation experiments show that cloche acts cell-autonomously within the endothelial lineage. To analyze further the role of cloche in regulating endothelial cell differentiation, we have examined the expression of flk-1 and tie, two receptor tyrosine kinase genes expressed early and sequentially in the endothelial lineage. In wild-type fish, flk-1-positive cells are found throughout the embryo and differentiate to form the nascent vasculature. In cloche mutants, flk-1-positive cells are found only in the lower trunk and tail regions, and this expression is delayed as compared to wild-type. Unlike the flk-1-positive cells in wild-type embryos, those in cloche mutants do not go on to express tie, suggesting that their differentiation is halted at an early stage. We also find that the cloche mutation is not linked to flk-1. These data indicate that cloche affects the differentiation of all endothelial cells and that it acts at a very early stage, either by directly regulating flk-1 expression or by controlling the differentiation of cells that normally develop to express flk-1.
cloche mutants also have a blood deficit and their hematopoietic tissues show no expression of the hematopoietic transcription factor genes GATA-1 or GATA-2 at early stages. Because the appearance of distinct levels of flk-1 expression is delayed in cloche mutants, we examined GATA-1 expression at late embryonic stages and found some blood cell differentiation that appears to be limited to the region lined by the flk-1-expressing cells. The spatial restriction of blood in the ventroposterior-most region of cloche mutant embryos may be indicative of a ventral source of signal(s) controlling hematopoietic differentiation. In addition, the restricted colocalization of blood and endothelium in cloche mutants suggests that important interactions occur between these two lineages during normal development.
A differential display strategy identifies Cryptic, a novel EGF-related gene expressed in the axial and lateral mesoderm during mouse gastrulation
Authors: Shen Michael M. , Wang Hongyu , Leder Philip 
Published: April 2021

ABSTRACT
We have developed a differential display screening approach to identify mesoderm-specific genes, relying upon the differentiation of embryonic stem (ES) cells in vitro. Using this strategy, we have isolated a novel murine gene that encodes a secreted molecule containing a variant epidermal growth factor-like (EGF) motif. We named this gene Cryptic, based on its predicted protein sequence similarity with Cripto, which encodes an EGF-related growth factor. Based on their strong sequence similarities, we propose that Cryptic, Cripto, and the Xenopus FRL-1 gene define a new family of growth factor-like molecules, which we name the ‘CFC’ (Cripto, Frl-1, and Cryptic) family. Analysis of Cryptic expression by in situ hybridization shows that it is expressed during gastrulation in two spatial domains that correspond to the axial and lateral mesoderm. In the first domain of expression, Cryptic expression is progressively localized to the anterior primitive streak, the head process, and the node and notochordal plate. In the second domain, Cryptic expression is initially concentrated in the lateral region of the egg cylinder, and is later found circumferentially in the intermediate and lateral plate mesoderm. Furthermore, Cryptic expression can also be detected at the early head-fold stage in the midline neuroectoderm, and consequently is an early marker for the prospective floor plate of the neural tube. Expression of Crypticceases at the end of gastrulation, and has not been observed in later embryonic stages or in adult tissues. Thus, Crypticencodes a putative signaling molecule whose expression suggests potential roles in mesoderm and/or neural patterning during gastrulation.
Pattern of differentiated nerve cells in hydra is determined by precursor migration
Authors: Hager Gundel , David Charles N. 
Published: April 2021

ABSTRACT
The nervous system of the fresh water polyp hydra is built up as a nerve net spread over the whole body, with higher densities in the head and the foot. In adult hydra, as a result of continuous growth, new nerve cell differentiation takes place continuously. The pattern of nerve cell differentiation and the role of nerve cell precursor migration in establishing the pattern have been observed in vivo by vitally labelling precursor cells with DiI. The results indicate that nerve cell precursors arise directly from stem cells, complete a final cell cycle and divide, giving rise to two daughter cells, which differentiate into nerve cells. A sub-population of the nerve cell precursors are migratory for a brief interval at the onset of the terminal cell cycle, then complete the cell cycle and divide at the site of differentiation. Labelling small patches of tissue in the head, body column and peduncle/foot with DiI indicated that formation of nerve cell precursors was nearly constant at all three positions. However, at least half of the labelled precursors in the body column migrated to the head or foot before differentiating; by contrast, precursors in head and foot differentiated in situ without significant migration. This redistribution leads to a net increase of nerve cell precursors in head and foot compared to body column and thus to the higher density of nerve cells in these regions.
The PAX gene egl-38 mediates developmental patterning in Caenorhabditis elegans
Authors: Chamberlin Helen M. , Palmer Robert E. , Newman Anna P. , Sternberg Paul W. , Baillie David L. , Thomas James H. 
Published: April 2021

ABSTRACT
Mutations in the C. elegans gene egl-38 result in a discrete set of defects in developmental pattern formation. In the developing egg-laying system of egl-38 mutant hermaphrodites, the identity of four uterine cells is disrupted and they adopt the fate of their neighbor cells. Likewise, the identity of two rectal epithelial cells in the male tail is disrupted and one of these cells adopts the fate of its neighbor cell. Genetic analysis suggests that the egl-38 functions in the tail and the egg-laying system are partially separable, as different egl-38 mutations can preferentially disrupt the different functions. We have cloned egl-38 and shown that it is a member of the PAX family of genes, which encode transcription factors implicated in a variety of developmental patterning events. The predicted EGL-38 protein is most similar to the mammalian class of proteins that includes PAX2, PAX5 and PAX8. The sequence of egl-38 mutant DNA indicates that the tissue-preferential defects of egl-38 mutations result from substitutions in the DNA-binding paired domain of the EGL-38 protein. egl-38 thus provides the first molecular genetic insight into two specific patterning events that occur during C. elegans development and also provides the opportunity to investigate the in vivo functions of this class of PAX proteins with single cell resolution.
Retrospective clonal analysis of the cerebellum using genetic laacZ/lacZ mouse mosaics
Authors: Mathis Luc , Bonnerot Claire , Puelles Luis , Nicolas Jean-François 
Published: April 2021

ABSTRACT
Analysis of lacZ neuronal clones in the mouse cerebellum demonstrates genealogical independence of the primary and secondary germinal epithelia (PGE and SGE) from early development. PGE precursors and their neuronal descendants are organised into two polyclonal groups of similar sizes that exhibit parasagittal patterning and generally respect the midline. The relationship between these two groups cannot be traced back in time to less than 80 independent cells, which were probably recruited following a period of non-coherent growth that distributes unrelated cells into distinct territories of the neural tube. A lateromedial clonal organisation is observed in the mature cerebellum, suggesting the existence of many small parasagittal domains of clonal restriction and/or of cell dispersion in the rostrocaudal but not in the mediolateral dimension. The organisation is orthogonal with respect to the cellular organisation in the neural tube as is the genetic organisation. Cellular and genetic patterning of the cerebellum therefore share similarities. A possible hypothesis is that distinct cell behaviours create the different clonal domains observed in this study and that the cellular and genetic organisation of the cerebellum are coordinated.
Bcl-2 is required for cranial sensory neuron survival at defined stages of embryonic development
Authors: Piñón Luzia G. P. , Middleton Gayle , Davies Alun M. 
Published: April 2021

ABSTRACT
To ascertain the role of endogenous Bcl-2 in maintaining the survival of developing neurons and modulating their responses to neurotrophins, we compared the in vitro and in vivo survival of cranial sensory neurons of wild-type and bcl-2 null mouse embryos. At the peak of naturally occurring neuronal death in the trigeminal ganglion at E14, trigeminal neurons from bcl-2−/− embryos initially survived in culture in response to NGF but were not sustained as well as neurons from wild-type embryos. At the end of the period of naturally occurring neuronal death at E18, Bcl-2-deficient trigeminal neurons survived with NGF as well as wild-type neurons. At E14 in vivo, the number of trigeminal neurons undergoing apoptosis was significantly greater in bcl-2−/−embryos, and there were significantly fewer neurons in the trigeminal ganglia of bcl-2−/− embryos at E16 and E18. Similar age-related changes in the responses of nodose ganglion neurons to BDNF were observed in cultures estab-lished from bcl-2−/− and wild-type embryos between E14 and E18. These results suggest that endogenous Bcl-2 is required for the sustained survival response of a subset of cranial sensory neurons to neurotrophins at particular stages of embryonic development and show that its absence leads to reduced numbers of these neurons in vivo.
Patterning the Xenopus blastula
Authors: Heasman Janet 
Published: April 2021

ABSTRACT
This review starts from the classical standpoint that there are at least two separable processes acting with respect to axis formation and tissue specification in the early Xenopus embryo: a UV-insensitive event establishing a postgastrula embryo consisting of three concentric germ layers, ectoderm, mesoderm and endoderm, all of a ventral character; and a UV-sensitive event producing tissue of a dorsal type, including somites, notochord and neural tissue, and concomitantly establishing the dorsoventral and anteroposterior axes. The experimental evidence suggesting the molecular basis of the dorsal and ventral pathways is reviewed.
Complex regulatory region mediating tailless expression in early embryonic patterning and brain development
Authors: Rudolph Karen M. , Liaw Gwo-Jen , Daniel Ann , Green Patricia , Courey Albert J. , Hartenstein Volker , Lengyel Judith A. 
Published: April 2021

ABSTRACT
tailless encodes a transcription factor expressed in multiple domains in the developing embryo. Early and transient expression at the posterior pole is required to establish a domain from which the eighth abdominal segment, telson and posterior gut arise. Just a few nuclear cycles later, a brain-specific domain is initiated at the anterior; expression in this domain is maintained with complex modulations throughout embryogenesis. Expression of tailless in this domain is required to establish the most anterior region of the brain. To understand the function and regulation of these different domains of expression, we provide a detailed description of tailless expression in brain neuroblasts and show that this expression is not detectably regulated by the head gap genes buttonhead or orthodenticle, by the proneural gene lethal of scuteor by taillessitself. We show that approximately 6 kb of sequenced upstream regulatory DNA can drive lacZ expression in a pattern that mimics the full tailless embryonic expression pattern. Within this sequence we identify multiple modules responsible for different aspects of thetaillesspattern. In addition to identifying additional torso response elements that mediate early blastoderm polar expression, we show that the complex brain expression pattern is driven by a combination of modules; thus expression at a low level through-out the brain and at a high level in the dorsal medial portion of the brain and in the optic lobe, as well as neuro-blast-specific repression are mediated by different DNA regions.
Timing and pattern of cell fate restrictions in the neural crest lineage
Authors: Henion Paul D. , Weston James A. 
Published: April 2021

ABSTRACT
The trunk neural crest of vertebrate embryos is a transient collection of precursor cells present along the dorsal aspect of the neural tube. These cells migrate on two distinct pathways and give rise to specific derivatives in precise embryonic locations. One group of crest cells migrates early on a ventral pathway and generates neurons and glial cells. A later-dispersing group migrates laterally and gives rise to melanocytes in the skin. These observations raise the possibility that the appearance of distinct derivatives in different embryonic locations is a consequence of lineage restrictions specified before or soon after the onset of neural crest cell migration.
To test this notion, we have assessed when and in what order distinct cell fates are specified during neural crest development. We determined the proportions of different types of precursor cells in cultured neural crest populations immediately after emergence from the neural tube and at intervals as development proceeds. We found that the initial neural crest population was a heterogeneous mixture of precursors almost half of which generated singlephenotype clones. Distinct neurogenic and melanogenic sublineages were also present in the outgrowth population almost immediately, but melanogenic precursors dispersed from the neural tube only after many neurogenic precursors had already done so. A discrete fate-restricted neuronal precursor population was distinguished before entirely separate fate-restricted melanocyte and glial precursor populations were present, and well before initial neuronal differentiation. Taken together, our results demonstrate that lineage-restricted subpopulations constitute a major portion of the initial neural crest population and that neural crest diversification occurs well before overt differentiation by the asynchronous restriction of distinct cell fates. Thus, the different morphogenetic and differentiative behavior of neural crest subsets in vivo may result from earlier cell fate-specification events that generate developmentally distinct subpopulations that respond differentially to environmental cues.
punt and schnurri regulate a somatically derived signal that restricts proliferation of committed progenitors in the germline
Authors: Matunis Erika , Tran John , Gönczy Pierre , Caldwell Kim , DiNardo Stephen 
Published: April 2021

ABSTRACT
To identify regulators of stem cell lineages, we are focusing on spermatogenesis in Drosophila. In spermatogenesis, each germline stem cell divides asymmetrically, renewing itself and producing a transiently amplifying daughter, which divides four times. By screening for mutants in which daughter cells fail to stop dividing, we find that the TGF-β signal transducers schnurri and punt are required to limit transient amplification of germ cells. Mosaic analysis demonstrates that punt and schnurri act within somatic cyst cells that surround germ cells, rather than in germ cells. Thus, a cyst-cell-derived signal restricts germ cell proliferation and this signal is initiated by input from a member of the TGF-β superfamily. Thus, a signal relay regulates progression through the germline stem cell lineage.
Relationship between dose, distance and time in Sonic Hedgehog-mediated regulation of anteroposterior polarity in the chick limb
Authors: Yang Y. , Drossopoulou G. , Chuang P.-T. , Duprez D. , Marti E. , Bumcrot D. , Vargesson N. , Clarke J. , Niswander L. , McMahon A. , Tickle C. 
Published: April 2021

ABSTRACT
Anteroposterior polarity in the vertebrate limb is thought to be regulated in response to signals derived from a specialized region of distal posterior mesenchyme, the zone of polarizing activity. Sonic Hedgehog (Shh) is expressed in the zone of polarizing activity and appears to mediate the action of the zone of polarizing activity. Here we have manipulated Shh signal in the limb to assess whether it acts as a longrange signal to directly pattern all the digits. Firstly, we demonstrate that alterations in digit development are dependent upon the dose of Shh applied. DiI-labeling experiments indicate that cells giving rise to the extra digits lie within a 300 μm radius of a Shh bead and that the most posterior digits come from cells that lie very close to the bead. A response to Shh involves a 12-16 hour period in which no irreversible changes in digit pattern occur. Increasing the time of exposure to Shh leads to specification of additional digits, firstly digit 2, then 3, then 4. Cell marking experiments demonstrate that cells giving rise to posterior digits are first specified as anterior digits and later adopt a more posterior character. To monitor the direct range of Shh signalling, we developed sensitive assays for localizing Shh by attaching alkaline phosphatase to Shh and introducing cells expressing these forms into the limb bud. These experiments demonstrate that long-range diffusion across the anteroposterior axis of the limb is possible. However, despite a dramatic difference in their diffusibility in the limb mesenchyme, the two forms of alkaline phosphatase-tagged Shh proteins share similar polarizing activity. Moreover, Shh-N (aminoterminal peptide of Shh)-coated beads and Shh-expressing cells also exhibit similar patterning activity despite a significant difference in the diffusibility of Shh from these two sources. Finally, we demonstrate that when Shh-N is attached to an integral membrane protein, cells transfected with this anchored signal also induce mirror-image pattern duplications in a dose-dependent fashion similar to the zone of polarizing activity itself. These data suggest that it is unlikely that Shh itself signals digit formation at a distance. Beads soaked in Shh-N do not induce Shh in anterior limb mesenchyme ruling out direct propagation of a Shh signal. However, Shh induces dose-dependent expression of Bmp genes in anterior mesenchyme at the start of the promotion phase. Taken together, these results argue that the dose-dependent effects of Shh in the regulation of anteroposterior pattern in the limb may be mediated by some other signal(s). BMPs are plausible candidates.
Mutations in the HYDRA1 gene of Arabidopsis perturb cell shape and disrupt embryonic and seedling morphogenesis
Authors: Topping Jennifer F. , May Vanessa J. , Muskett Paul R. , Lindsey Keith 
Published: April 2021

ABSTRACT
Mutations in the HYDRA1 (HYD1) gene of Arabidopsis thaliana can prevent normal morphological development of embryos and seedlings. Three allelic mutants (hydra 1-1, hydra1-2 and hydra1-3) have been identified, and in each the seedling is characterized by having a variable number of cotyledons, a short and wide hypocotyl and a much reduced root system. hydra1 embryos appear to develop normally to the octant stage, but fail to establish a distinct protoderm and lack bilateral symmetry, developing multiple cotyledonary primordia of irregular size and shape. Cells of the embryo proper, but not the suspensor, exhibit abnormalities in size and shape. The hydra1 embryo fails to develop an embryonic root, but embryos and seedlings express molecular markers of apical-basal polarity. Mutant seedlings produce leaves to form a small cabbage-like habit and may occasionally produce sterile flowers, though the mutation is commonly seedling-lethal. hydra1 seedlings exhibit abnormal radial patterning, but nevertheless express at least one molecular marker of vascular cell differentiation. A model is proposed in which the HYDRA1 protein functions as an essential component of the cell expansion system.
Regulation of segmentation and segmental identity by Drosophila homeoproteins: the role of DNA binding in functional activity and specificity
Authors: Biggin Mark D. , McGinnis William 
Published: April 2021

ABSTRACT
Recent advances have shed new light on how the Q50 homeoproteins act in Drosophila. These transcription factors have remarkably similar and promiscuous DNA-binding specificities in vitro; yet they each specify distinct developmental fates in vivo. One current model suggests that, because the Q50 homeoproteins have distinct biological functions, they must each regulate different target genes. According to this ‘co-selective binding’ model, significant binding of Q50 homeoproteins to functional DNA elements in vivo would be dependent upon cooperative interactions with other transcription factors (cofactors). If the Q50 homeoproteins each interact differently with cofactors, they could be selectively targeted to unique, limited subsets of their in vitro recognition sites and thus control different genes. However, a variety of experiments question this model. Molecular and genetic experiments suggest that the Q50 homeoproteins do not regulate very distinct sets of genes. Instead, they mostly control the expression of a large number of shared targets. The distinct morphogenic properties of the various Q50 homeoproteins may principally result from the different manners in which they either activate or repress these common targets. Further, in vivo binding studies indicate that at least two Q50 homeoproteins have very broad and similar DNA-binding specificities in embryos, a result that is inconsistent with the ‘co-selective binding’ model. Based on these and other data, we suggest that Q50 homeoproteins bind many of their recognition sites without the aid of cofactors. In this ‘widespread binding’ model, cofactors act mainly by helping to distinguish the way in which homeoproteins regulate targets to which they are already bound.
PAX2 is expressed in multiple spinal cord interneurons, including a population of EN1+ interneurons that require PAX6 for their development
Authors: Burrill John D. , Moran Laura , Goulding Martyn D. , Saueressig Harald 
Published: April 2021

ABSTRACT
Members of the PAX family of transcription factors are candidates for controlling cell identity in the spinal cord. We have morphologically analyzed cells that express one of these transcription factors, PAX2, demonstrating multiple interneuron cell types express PAX2. Two ventral populations of PAX2-expressing interneurons in the spinal cord are marked by coexpression of the transcription factors, EN1 and EVX1. Interestingly, the expression domains of PAX2, EN1 and EVX1 in postmitotic neurons correlate closely with those of Pax6 and Pax7 in the ventricular zone, implicating these patterning genes in the regulation of PAX2, EN1 and EVX1. We show that one of these patterning genes, Pax6, is required for the correct specification of ventral PAX2+ interneurons that coexpress EN1. These results demonstrate that the early activity of patterning genes in the ventricular zone determines interneuron identity in the spinal cord.