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C H Koster

Publications and source records attributed to C H Koster.

9 recordsLinked to original sources
PubMed1998

Graded retinoid responses in the developing hindbrain.

The purpose of this study was to make an explicit test of the idea that a retinoid could act as a morphogen, differentially activating genes and specifying anteroposterior (a-p) level in the developing vertebrate central nervous system (CNS). Our approach was to characterize the concentration-dependent effects of retinoic acid (RA) on the neural expression of a set of a-p patterning genes, both in vivo and in an in vitro system for neural patterning. Our results indicate that a retinoid is unlikely to specify a-p level along the entire CNS. Instead, our data support the idea that the developing hindbrain may be patterned by a retinoid gradient. Sequentially more posterior hindbrain patterning genes were induced effectively by sequentially higher RA concentration windows. The most posterior CNS level induced under our RA treatment conditions corresponded to the most posterior part of the hindbrain.

Animals↗
PubMed1998

Inhibition of retinoic acid receptor-mediated signalling alters positional identity in the developing hindbrain.

Retinoids regulate gene expression via nuclear retinoic acid receptors, the RARs and RXRs. To investigate the functions of retinoid receptors during early neural development, we expressed a dominant negative RARbeta in early Xenopus embryos. We obtained evidence that dominant negative RARbeta specifically inhibits RAR/RXR heterodimer-mediated, but not RXR homodimer-mediated, transactivation. Both all-trans- and 9-cis-RA-induced teratogenesis were, however, efficiently opposed by ectopic expression of dominant negative RARbeta, indicating that only RAR/RXR transactivation is required for retinoid teratogenesis by each of these ligands. Experiments with two RXR-selective ligands confirmed that activation of RXR homodimers does not cause retinoid teratogenesis. Dominant negative RARbeta thus specifically interferes with the retinoid signalling pathway that is responsible for retinoid teratogenesis. Dominant negative RARbeta-expressing embryos had a specific developmental phenotype leading to disorganization of the hindbrain. Mauthner cell multiplications in the posterior hindbrain, and (both anteriorly and posteriorly) expanded Krox-20 expression domains indicated (partial) transformation of a large part of the hindbrain into (at least partial) rhombomere 3, 4 and/or 5 identity. In contrast, the fore- and midbrain and spinal cord appeared to be less affected. These data indicate that RARs play a role in patterning the hindbrain.

Alitretinoin↗
PubMed1995

Intracellular acidification of gastrula ectoderm is important for posterior axial development in Xenopus.

There is evidence suggesting that pHi elevation can induce differentiation to cement gland, an extremely anterior structure, during the early development of Xenopus laevis (Picard, J. J. (1975) J. Embryol. exp. Morphol. 33, 957-967; Sive, H. L., Hattori, K. and Weintraub, H. (1989) Cell 58, 171-180). We wanted to investigate whether axial development or neural induction are mediated in Xenopus via regulation of pHi. Our interest was stimulated further because certain signal transduction pathways, which are thought to mediate anterior neural induction (Otte, A. P., Van Run, P., Heideveld, M., Van Driel, R. and Durston, A. J. (1989) Cell 58, 641-648; Durston and Otte (1991), Cell-Cell Interactions in Early Development, pp. 109-127), are also known to modify the activity of proton extruders (Mitsuka and Berk (1991) Am. J. Physiol. 260, C562-C569; Wakabayashi, S., Sardet, C., Fafournoux, P., Counillon, L., Meloche, S., Pages, G. and Pouysségur, J. (1993) Rev. Physiol. Biochem. Pharmacol. Vol. 119, pp. 157-186). We therefore measured pHi in explants of gastrula ectoderm and neurectoderm and identified ion exchangers that regulate pHi in these tissues. The measurements showed that pHi decreases in explants of both neurectoderm and uninduced ectoderm during the time course of gastrulation, this pHi decrease thus fails to correlate with neural induction. One important regulator of this cytoplasmic acidification is the Na+/H+ exchanger. The pHi set point, at which the acid extrusion activity of this alkalizing exchanger is shut off, shifts to more acidic values during the time course of gastrulation, thus permitting cytoplasmic acidification. We found also that preventing cytoplasmic acidification and thereby elevating pHi in late gastrula cells led to the specific suppression of posterior development. Neural induction and anterior development were unaffected by treatments leading either to an elevation of or a decrease in pHi. These findings indicate that the cellular processes mediating anterior development and neural induction are pHi tolerant, while the signals mediating posterior development require a sustained pHi decrease for their action, suggesting that downregulation of pHi is necessary for posterior axial development.

Animals↗
PubMed1990

Activin-like factor from a Xenopus laevis cell line responsible for mesoderm induction.

Induction of mesoderm during early amphibian embryogenesis can be mimicked in vitro by adding growth factors, including heparin-binding and type-beta transforming growth factors (TGF-beta), to isolated ectoderm explants from Xenopus laevis embryos. Although the mesoderm-inducing factor (MIF) from X. laevis XTC cells (XTC-MIF) has properties similar to TGF-beta, this factor is still unidentified. Recently, we obtained a number of homogeneous cell lines from the heterogeneous XTC population, which differ in their MIF production. Only one, XTC-GTX-11, produced MIF, although it was similar to the rest of the clones in its production of known growth factors, including TGF-beta activity. This observation, together with the identification of activin A as a potent MIF led us to study the parallel activities of MIF and activin. Here we report an analysis of activin-like activity from XTC cells and some of the XTC clones, including XTC-GTX-11. There is a clear consistent correlation between MIF activity and presence of activin activity, indicating that XTC-MIF is the Xenopus homologue of mammalian activin.

Activins↗
PubMed1990

Effects of cell heterogeneity on production of polypeptide growth factors and mesoderm-inducing activity by Xenopus laevis XTC cells.

The Xenopus laevis XTC cell line has been analyzed for the production of polypeptide growth factors and mesoderm-inducing activity. By the use of specific biological assays, it is shown that XTC cells produce a growth factor functionally related to the platelet-derived growth factor (PDGF) and two transforming growth factor (TGF) beta-like activities. Mesoderm-inducing activity, as measured on X. laevis ectodermal explants from stage 10 embryos, was found to coelute on a Bio-Gel P-100 column with one of the TGF beta-like activities at an apparent molecular weight of 6-10 kDa. Analysis of the DNA content from XTC cells by flow cytometry demonstrated that the cell line is heterogeneous and consists of both tetraploid and diploid cells. Cloning of the XTC cells and selecting single-cell colonies on the basis of their ability to grow in soft agar resulted in the isolation of several homogeneous, morphologically different clonal derivatives. Analysis of conditioned medium from these clonal derivatives showed that only one of them, the only diploid line among six investigated, produced a strong heat- and acid-stable mesoderm-inducing activity that induced notochord and muscle formation in stage 10 X. laevis ectodermal explants. The relation between this activity and a recently described TGF beta-like mesoderm-inducing factor obtained from XTC-conditioned medium will be discussed. In conclusion, a clonal cell line derived from X. laevis XTC cells which provides a good source for further characterization of mesoderm-inducing factors has been established.

Animals↗
PubMed1990

Characterization of a maternal type VI collagen in Xenopus embryos suggests a role for collagen in gastrulation.

We characterized a novel extracellular matrix element that is present in the earliest developmental stages of Xenopus laevis, and is recognized by an mAb 3D7. Based on amino acid composition, breakdown patterns by bacterial collagenases, and the molecular weights of the components of the antigen (240, 200, and 140 kD), we found it very similar to mammalian collagen type VI. The antigen is evenly distributed in unfertilized eggs. Shortly after fertilization, it becomes localized intracellularly in the periphery of the cleaving embryo as well as in the extracellular spaces. During gastrulation, the antigen was localized in the cells lining the blastopore and in the extracellular space between the two cell layers, in the presumptive archenteron. When Fab elements of the 3D7 antibody were added to the culture medium, gastrulation was blocked, suggesting a role for the antigen in gastrulation movements.

Amino Acids↗
PubMed1988

Protein kinase C mediates neural induction in Xenopus laevis.

Inductive cell interactions are essential in early embryonic development, but virtually nothing is known about the molecular mechanisms involved. Recently factors resembling fibroblast growth factor and transforming growth factor-beta were shown to be involved in mesoderm induction in Xenopus laevis, suggesting that membrane receptor-mediated signal transduction is important in induction processes. Here we report direct measurements of protein kinase C (PKC) activity in uninduced ectoderm, and in neuroectoderm shortly after induction by the involuting mesoderm, in Xenopus laevis embryos. Membrane-bound PKC activity increased three to fourfold in the induced neuroectoderm while the cytosolic PKC activity was decreasing, indicating that PKC activity was translocated during neural induction. A similar time- and dose-dependent translocation of activity was seen after incubation with the PKC activator 12-O-tetradecanoyl phorbol-13-acetate, which also induced neural tissue in competent ectoderm, suggesting that PKC is involved in the response to the endogenous inducing signal during neural induction.

Animals↗
PubMed1983

Evidence for a functional role of the cytoskeleton in determination of the dorsoventral axis in Xenopus laevis eggs.

A normal table of events of the first cleavage period in the fertilized egg (cf. Gerhart, 1980) has been completed (cf. Table I) by studying external and internal features. Through a cytological study of eggs fixed after video time-lapse observation such features can directly be correlated and it has been shown that the first postfertilization wave (PFW) reflects spermaster growth, which causes rearrangements of animal yolk material. This may, in conjunction with the interaction of the spermaster rays with the cortex, define, in time as well as in space, the asymmetric cortical contraction which we suppose to evoke asymmetry in the animal hemisphere by formation of the vitelline wall (Pasteels, 1964) and in the vegetal hemisphere by formation of the Vegetal Dorsalising Centre (Kirschner et al. 1981). Neither prick-activated eggs nor fertilized eggs incubated in vinblastine develop a spermaster. Under these conditions abnormal cytoplasmic segregation may be directed by gravity alone. For normal development the activated egg must in some way, for instance through the sperm centriole, organize microtubule assembly into a monaster. The centriole acts as a microtubule-organizing centre in structuring the egg's cytoskeleton, and through this directs localization of the various yolk components, in time as well as in space. In egg rotation experiments performed under appropriate conditions, the cytoskeleton is disturbed and yolk rearranges under gravity till a new equilibrium is established which determines a new dorsoventral polarity. Such experiments also show that neither the dorsal cytoplasm nor the grey crescent cortex act as the ultimate dorsal determinants, since their localization is unaltered upon rotation, whereas the overall yolk distribution is significantly changed.

Animals↗