bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a homolog of human bone morphogenetic protein 1 in the embryo of the sea urchin, Strongylocentrotus purpuratus
Authors: Hwang Sheng-Ping L. , Partin Jacqueline S. , Lennarz William J. 
Published: April 2021

ABSTRACT
A cDNA clone encoding a protein homologous to human bone morphogenetic protein 1 (huBMP1) was isolated from a sea urchin embryo cDNA library. This sea urchin gene, named suBMP, encodes a protein of Mr of 72×103. The deduced amino acid sequence of suBMP shares 72% sequence similarity (55% identity) with that of huBMP1. Like huBMP1 it also contains an N-terminal metalloendo-protease domain that shares sequence similarity with the astacin protease from crayfish, a C-terminal domain that is similar to the repeat domain found in C1r or C1s serine proteases, and an EGF-like segment. Although suBMP mRNA was detectable at a low level in the unfertilized egg, maximal expression of mRNA was observed at hatched blastula stage, with only a modest decrease in level at later stages of development. In situ hybridization studies revealed that suBMP mRNA is found in both ectodermal and primary mesenchyme cells in hatched blastula-stage embryos. Maximal expression of suBMP was observed at mesenchyme blastula, just before the onset of primitive skeleton (spicule) formation. SuBMP was found by immunoelectronmicroscopy in all cell types in late gastrula stage embryos. The antibody gold particles appeared in small clusters in the cytoplasm, on the surface of the cells and within the blastocoel. This distribution of suBMP, coupled with the finding that it was associated with membranes but was released by sodium carbonate treatment, suggests that the protein is secreted, and subsequently associates with a cell surface component. Two models for the possible function of suBMP in spiculogenesis in the sea urchin embryo are discussed.
Induction of a second neural axis by the mouse node
Authors: Beddington Rosa S. P. 
Published: April 2021

ABSTRACT
The anterior aspect of the mouse primitive streak resembles the organizer of Xenopus and chick in terms of its developmental fate, ability to alter pattern in the chick limb bud and with respect to the repertoire of genes that its constituent cells express. However, until now there has been no direct evidence that the mouse node organizes pattern during gastrulation, nor that the exceptionally small mouse embryonic egg cylinder can be induced to form a second axis. Grafts of transgenically marked mid-gastrulation mouse node, or node labelled with DiI, to a posterolateral location in a host embryo of the same developmental stage results in the induction of a second neural axis and the formation of ectopic somites. The graft gives rise predominantly to notochord and endoderm tissue whereas the neurectoderm and somites are mainly of host origin. The ectopic notochord formed is derived solely from the donor node which suggests that the node can serve as a ‘stem cell’ source of axial mesoderm. This is corroborated by the observation that labelling in situ the population of cells on the outer surface of the mid-gastrulation node with DiI results in continuous labelling of the notochord. DiI-labelled cells are present throughout the notochord from a rostral boundary in the cranial region to its most caudal extreme and the node itself always remains labelled.
Abnormal embryonic cerebellar development and patterning of postnatal foliation in two mouse Engrailed-2 mutants
Authors: Millen Kathleen J. , Wurst Wolfgang , Herrup Karl , Joyner Alexandra L. 
Published: April 2021

ABSTRACT
The cerebellum is an ideal system to study pattern formation in the central nervous system because of its simple cytoarchitecture and regular organization of folds and neural circuitry. Engrailed-2 (En-2) is expressed in a spatially restricted broad band around the mesencephalic-metencephalic junction, a region from which the cerebellum is derived. Mice homozygous for a targeted deletion of the En-2 homeobox, En-2hd, previously have been shown to have an altered adult cerebellar foliation pattern. To address whether the En-2hd allele was hypomorphic, we generated a putative null mutation that makes an N-terminal deletion (ntd). Mice homozygous for this new mutation, En-2ntd, display an identical cerebellar patterning defect, suggesting that both alleles represent null alleles. We also examined the developmental profile of En-2 homozygous mutant cerebellar foliation. This revealed a complex phenotype of general developmental delay and abnormal formation of specific fissures with the most severe morphological disruptions being limited to the posterior region of the cerebellum. The expression of two transgenes, which express lacZ in lobe-specific patterns in the cerebellum, also was found to be altered in En-2 homozygotes, suggesting possible lobe transformations. Finally, during embryogenesis there was a clear delay in fusion of the cerebellar rudiments at the midline by 15.5 d.p.c. This and the expression pattern of En-2 suggests that although cerebellar foliation is largely a postnatal process, the patterning of the cerebellum may begin during embryogenesis and that En-2 plays a critical role in this early process.
The Caenorhabditis elegans gene lin-44 controls the polarity of asymmetric cell divisions
Authors: Herman Michael A. , Horvitz H. Robert 
Published: April 2021

ABSTRACT
The generation and orientation of cellular and organismic polarity are fundamental aspects of development. Mutations in the gene lin-44 of the nematode Caenorhabditis elegans reverse both the relative positions of specific sister cells and the apparent polarities of these cells. Thus, lin-44 mutants appear to generate polar cells but to misorient these cells along the body axis of the animal. We postulate that lin-44 acts to specify the orientation of polar cells.
Inhibition of myogenic differentiation in myoblasts expressing a truncated type II TGF-β receptor
Authors: Filvaroff Ellen H. , Ebner Reinhard , Derynck Rik 
Published: April 2021

ABSTRACT
Transforming growth factor-β (TGF-β? is thought to play a role in mesenchymal cell development and, specifically, in muscle differentiation, yet its precise role in the latter process remains unclear. TGF-β has been shown to both inhibit and induce myoblast maturation in vitro, depending on the culture conditions. Whether the type I or type II TGF-β receptor mediates the various TGF-β effects on myogenesis is not known. In the present study, C2C12 myoblasts were transfected with an expression vector for a truncated type II TGF-β receptor, which has been shown to act as a dominant negative inhibitor of type II receptor signaling. In contrast to the parental cells, the transfected clones did not efficiently form myotubes or induce expression of MyoD, myogenin and several other differentiation markers following incubation in low serum media. However, some muscle differentiation markers continued to be expressed in the transfected cells suggesting that at least two pathways are involved in muscle cell differentiation. These cells could still growth arrest in low serum media, showing that decreased proliferation can be dissociated from differentiation. Unlike several oncogenes known to block myogenic differentiation, expression of the truncated TGF-β receptor did not result in myoblast transformation. Injection of the parental or the transfected C2C12 cells into the limb muscle of nude mice revealed quantitative and qualitative differences in their behavior, and suggested that myoblasts expressing the truncated TGF-β receptor cannot fuse in vivo. Finally, retrovirusmediated expression of MyoD in the transfected cells restored their ability to form myotubes in vitro, indicating that inhibition of myoblast differentiation by the truncated TGF-β receptor may depend on decreased MyoD expression. We propose that TGF-β signaling through the type II receptor is required for several distinct aspects of myogenic differentiation and that TGF-β acts as a competence factor in this multistep process.
The cleavage stage origin of Spemann’s Organizer: analysis of the movements of blastomere clones before and during gastrulation in Xenopus
Authors: Bauer Daniel V. , Huang Sen , Moody Sally A. 
Published: April 2021

ABSTRACT
Recent investigations into the roles of early regulatory genes, especially those resulting from mesoderm induction or first expressed in the gastrula, reveal a need to elucidate the developmental history of the cells in which their transcripts are expressed. Although fates both of the early blastomeres and of regions of the gastrula have been mapped, the relationship between the two sets of fate maps is not clear and the clonal origin of the regions of the stage 10 embryo are not known. We mapped the positions of each blastomere clone during several late blastula and early gastrula stages to show where and when these clones move. We found that the dorsal animal clone (A1) begins to move away from the animal pole at stage 8, and the dorsal animal marginal clone (B1) leaves the animal cap by stage 9. The ventral animal clones (A4 and B4) spread into the dorsal animal cap region as the dorsal clones recede. At stage 10, the ventral animal clones extend across the entire dorsal animal cap. These changes in the blastomere constituents of the animal cap during epiboly may contribute to the changing capacity of the cap to respond to inductive growth factors. Pregastrulation movements of clones also result in the B1 clone occupying the vegetal marginal zone to become the primary progenitor of the dorsal lip of the blastopore (Spemann’s Organizer). This report provides the fundamental descriptions of clone locations during the important periods of axis formation, mesoderm induction and neural induction. These will be useful for the correct targeting of genetic manipulations of early regulatory events.
A role for cytoplasmic determinants in mesoderm patterning: cell-autonomous activation of the goosecoid and Xwnt-8 genes along the dorsoventral axis of early Xenopus embryos
Authors: Lemaire P. , Gurdon J. B. 
Published: April 2021

ABSTRACT
Although an induction event is required for the formation of mesoderm in Xenopus embryos, it is not clear that this induction is wholly sufficient to give rise to a correctly patterned mesodermal layer. We have studied the expression of the two genes, goosecoid and Xwnt-8, in Xenopus gastrulae in which cell-cell communication, and therefore mesoderm induction, has been prevented by frequent cell dispersion. Although neither the early panmesodermal marker Xbra nor the muscle-specific α-actin gene were activated under these conditions, goosecoid and Xwnt-8 were activated in cells of dorsal and ventrolateral origin respectively, thus correctly reflecting their distribution during normal development. We also show that the spatial pattern of expression of these two genes along the animal-vegetal axis is similar in normal and in dissociated early gastrulae: goosecoid is mainly expressed in future mesoderm while the domain of expression of Xwnt-8 spans the mesoderm-endoderm boundary. These results show that, during the blastula and early gastrula stages, gene activation can be controlled cell-autonomously along both the animal-vegetal and dorsoventral embryo axes. This suggests that the inheritance of localised maternal cytoplasmic determinants is a key event for the patterning of mesoderm. We present a modified model of mesoderm formation in which the different mesoderm cell types are produced as a result of cooperation between inductiondependent and induction-independent immediate-early genes.
Null alleles reveal novel requirements for Bic-D during Drosophila oogenesis and zygotic development
Authors: Ran Bing , Bopp Rita , Suter Beat 
Published: April 2021

ABSTRACT
In the Drosophila ovary, the Bicaudal-D (Bic-D) gene is required for the differentiation of one of 16 interconnected cystocyte sister cells into an oocyte. A new class of Bic-Dnull alleles reveals a novel requirement for Bic-D for zygotic viability. In the germ line, the null mutations show that developmental processes that take place in germarial region 1, even those that create asymmetry, are independent of Bic-D function. Bic-D is then required to establish oocyte identity in one cystocyte and is essential, not only for the oocyte-specific accumulation of all oocyte markers that we have tested so far, but also for the posterior migration of the oocyte. In addition, normal polarity amongst the nurse cells requires Bic-D, indicating that the creation of different nurse cell identities may depend on oocyte determination. Our results show that different processes in early oogenesis require different amounts of Bic-D in a processspecific way and certain later processes can proceed at low levels of Bic-D. This suggests that the patterning of the female germ line and the development of an oocyte depend on differential responses to a single activity that is capable of initiating distinct oogenesis processes and can establish different cell fates.
Tissue and cellular patterning of the musculature in chick wings
Authors: Robson L. G. , Kara T. , Crawley A. , Tickle C. 
Published: April 2021

ABSTRACT
Development of the musculature involves generation of a precise number of individual muscles arranged in appropriate locations, each with the correct cellular patterning. To find out the rules that govern muscle number and arrangement, the forearm musculature of chick wing buds was analysed following grafts of the polarizing region or application of retinoic acid. Muscle patterns appear symmetrical with ‘posterior’ muscles now forming in the anterior part of the wing. When the number of muscles that develop is reduced, pattern symmetry is maintained, with loss of anterior muscles in the mid-line, especially dorsally. Strict anteroposterior ordering of muscles in duplicated patterns does not always occur. The number of muscles that develops bears some relationship to the number of forearm elements. Each muscle has a characteristic pattern of fast and slow fibres. In duplicated wings, each pair of symmetrically arranged muscles has the same fibre type pattern. Not only are proportions of fast and slow fibres similar, but local variations in fibre type arrangement within the muscle are also reproduced. This suggests that the cellular pattern within the new ‘posterior’ muscles at the anterior of the limb has been re-specified. In manipulated limb buds, which will develop a duplicated muscle pattern, there are no detectable changes in distribution and number of potentially myogenic cells, and fibre type patterning within early muscle masses also appears normal. In contrast, the splitting process that divides up muscle masses is altered. The appropriate fibre type arrangement only emerges after splitting is complete. This suggests that tissue patterning and cellular patterning occur at different times during muscle development.
msd is required for mesoderm induction in mice
Authors: Holdener Bernadette C. , Faust Cynthia , Rosenthal Nancy S. , Magnuson Terry 
Published: April 2021

ABSTRACT
Mesoderm induction is fundamental for establishing the basic body plan of the vertebrate embryo and mutations are critical for dissecting this process. Mouse embryos lacking msd (mesoderm deficiency) do not produce mesoderm but have well-defined extraembryonic and thickened embryonic ectoderm. Distribution of transcripts indicate that temporal regulation of gene expression relevant to gastrulation has begun but primitive-streak formation and mesoderm induction are blocked. Both msd-deficient embryos and embryonic stem (ES) cells fail to form highly differentiated structures of mesoderm origin, but are capable of ectodermal differentiation. Thus, the effects of the msd mutation are restricted to mesoderm formation and could result from the inability to respond to an inducing signal.
Mechanisms of cell rearrangement and cell recruitment in Drosophila ovary morphogenesis and the requirement of bric à brac
Authors: Godt Dorothea , Laski Frank A. 
Published: April 2021

ABSTRACT
The Drosophila ovary consists of repeated units, the ovarioles, where oogenesis takes place. The repetitive structure of the ovary develops de novo from a mesenchymal cell mass, a process that is initiated by the formation of a two-dimensional array of cell stacks, called terminal filaments, during the third larval instar. We have studied the morphogenetic process leading to the formation of terminal filaments and find that this involves recruitment, intercalation and sorting of terminal filament cells. Two other types of cell stacks that participate in ovary morphogenesis, the basal stalks and interfollicular stalks, also form by cell rearrangement utilizing a convergence and extension mechanism. Terminal filament formation depends on the Bric à brac protein, which is expressed in the nuclei of terminal filament cells and is cell autonomously required. Disruption of terminal filament formation, together with defects of basal and interfollicular stalk development, leads to disruption of ovariole formation and female sterility in bric à brac mutants.
Neurogenic genes control gene expression at the transcriptional level in early neurogenesis and in mesectoderm specification
Authors: D. Martín-Bermudo María , Carmena Ana , Jiménez Fernando 
Published: April 2021

ABSTRACT
The development of the central nervous system in the Drosophila embryo is initiated by the acquisition of neural potential by clusters of ectodermal cells, promoted by the activity of proneural genes. Proneural gene function is antagonized by neurogenic genes, resulting in the realization of the neural potential in a single cell per cluster. To analyse the relationship between proneural and neurogenic genes, we have studied, in specific proneural clusters and neuroblasts of wild-type and neurogenic mutants embryos, the expression at the RNA and protein levels of lethal of scute, the most important known proneural gene in central neurogenesis. We find that the restriction of lethal of scute expression that accompanies the restriction of the neural potential to the delaminating neuroblast is regulated at the transcriptional level by neurogenic genes.
These genes, however, do not control the size of proneural clusters. Morover, available antibodies do not provide evidence for an hypothetical posttranscriptional regulation of proneural proteins by neurogenic genes. We also find that neurogenic genes are required for the specification of the mesectoderm. This has been shown for neuralized and Notch, and could also be the case for Delta and for the Enhancer of split gene complex. Neurogenic genes would control at the transcriptional level the repression of proneural genes and the activation of single-minded in the anlage of the mesectoderm.
The Drosophila orphan nuclear receptor Seven-up requires the Ras pathway for its function in photoreceptor determination
Authors: Begemann Gerrit , Michon Anne-Marie , v.d.Voorn Loesje , Wepf Roger , Mlodzik Marek 
Published: April 2021

ABSTRACT
The Drosophila seven-up (svp) gene specifies outer photoreceptor cell fate in eye development and encodes an orphan nuclear receptor with two isoforms. Transient expression under the sevenless enhancer of either svp isoform leads to a dosage-dependent transformation of cone cells into R7 photoreceptors, and at a lower frequency, R7 cells into outer photoreceptors. To investigate the cellular pathways involved, we have taken advantage of the dosage sensitivity and screened for genes that modify this svp-induced phenotype. We show that an active Ras pathway is essential for the function of both Svp isoforms. Loss-of-function mutations in components of the Ras signal transduction cascade act as dominant suppressors of the cone cell transformation, whilst loss-of-function mutations in negative regulators of Ras-activity act as dominant enhancers. Furthermore, Svp-mediated transformation of cone cells to outer photoreceptors, reminiscent of its wildtype function in specifying R3/4 and R1/6 identity, requires an activated Ras pathway in the same cells, or alternatively dramatic increase in ectopic Svp protein levels. Our results indicate that svp is only fully functional in conjunction with activated Ras. Since we find that mutations in the Egfreceptor are also among the strongest suppressors of svpmediated cone cell transformation, we propose that the Ras activity in cone cells is due to low level Egfr signaling. Several models that could account for the observed svp regulation by the Ras pathway are discussed.
Mitotic delay dependent survival identifies components of cell cycle control in the Drosophila blastoderm
Authors: Ruden Douglas M. , Jäckle Herbert 
Published: April 2021

ABSTRACT
The Drosophila body pattern is laid down by maternal and zygotic factors which act during the early phase of embryonic development. During this period, nascent zygotic transcripts longer than about 6 kilobases are aborted between the rapid mitotic cycles. Resurrector1 (Res1) and Godzilla1 (God1), two newly identified dominant zygotic suppressor mutations, and a heterozygous maternal deficiency of the cyclin B locus, complement the partial loss of function of the segmentation gene knirps (kni) by extending the length of mitotic cycles at blastoderm. The mitotic delay caused by Res1 and God1 zygotically and by the deficiency of the cyclin B locus maternally allows the expression of a much longer transcript of a kni cognate gene normally aborted between the short mitotic cycles and consequently allows survival of kni mutant progeny. In addition to the practical benefits of identifying mutations in Drosophila cell cycle regulatory genes as suppressors of kni, our results have evolutionary implications regarding the flexibility of the genome to meet sudden selective pressures by recruiting cognate genes to function.
Disruption of the mouse RBP-Jк gene results in early embryonic death
Authors: Oka Chio , Nakano Toru , Wakeham Andrew , Pompa Jose Luis de la , Mori Chisato , Sakai Takashi , Okazaki Saeko , Kawaichi Masashi , Shiota Kohei , Mak Tak W. , Honjo Tasuku 
Published: April 2021

ABSTRACT
The RBP-Jк protein is a transcription factor that recog-nizes the sequence C(T)GTGGGGA. The RBP-Jк gene is highly conserved in a wide variety of species and the Drosophila homologue has been shown to be identical to Suppressor of Hairless [Su(H)] which plays important roles in the development of the peripheral nervous system. To explore the function of the RBP-Jк gene in mouse embryo-genesis, a mutation was introduced into the functional RBP-Jк gene in embryonic stem (ES) cells by homologous recombination. Null mutant ES cells survived but null mutant mice showed embryonic lethality before 10.5 days of gestation. The mutant mice showed severe growth retar-dation as early as 8.5 days of gestation. Developmental abnormalities, including incomplete turning of the body axis, microencephaly, abnormal placental development, anterior neuropore opening and defective somitogenesis, were observed in the mutant mice at 9.5 days of gestation. RBP-Jк mutant embryos expressed a posterior mesoder-mal marker FGFR1. Their irregularly shaped somites expressed a somite marker gene Mox 1 but failed to express myogenin. The RBP-Jк gene was revealed to be essential for postimplantation development of mice.