Biomedical subjects

G Howes

Publications and source records attributed to G Howes.

5 recordsLinked to original sources

PubMed1992

Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development.

The mesoderm of amphibian embryos such as Xenopus laevis arises through an inductive interaction in which cells of the vegetal hemisphere of the embryo act on overlying equatorial and animal pole cells. Three classes of 'mesoderm-inducing factor' (MIF) that might be responsible for this interaction in vivo have been discovered. These are members of the transforming growth factor type beta (TGF-beta), fibroblast growth factor (FGF) and Wnt families. Among the most potent MIFs are the activins, members of the TGF-beta family, but RNA for activin A and B is not detectable in the Xenopus embryo until neurula and late blastula stages, respectively, and this is probably too late for the molecules to act as natural inducers. In this paper, we use the polymerase chain reaction to clone additional members of the TGF-beta family that might possess mesoderm-inducing activity. We show that transcripts encoding Xenopus bone morphogenetic protein 4 (XBMP-4) are detectable in the unfertilized egg, and that injection of XBMP-4 RNA into the animal hemisphere of Xenopus eggs causes animal caps isolated from the resulting blastulae to express mesoderm-specific markers. Surprisingly, however, XBMP-4 preferentially induces ventral mesoderm, whereas the closely related activin induces axial tissues. Furthermore, the action of XBMP-4 is 'dominant' over that of activin. In this respect, XBMP-4 differs from basic FGF, another ventral inducer, where simultaneous treatment with FGF and activin results in activin-like responses. The dominance of XBMP-4 over activin may account for the ability of injected XBMP-4 RNA to 'ventralize' whole Xenopus embryos. It is interesting, however, that blastopore formation in such embryos can occur perfectly normally. This contrasts with embryos ventralized by UV-irradiation and suggests that XBMP-4-induced ventralization occurs after the onset of gastrulation.

Activins↗

PubMed1991

Inductive interactions in early embryonic development.

This is an update of a previous review (Current Opinion in Cell Biology 2:969-974) in which we discussed recent work attempting to understand the sequence of inductive interactions responsible for establishing the body plan of the early embryo. As before, we concentrate on inductive interactions in amphibian embryos, where significant progress has been made in the past two years. In this update, however, we also consider recent embryological data obtained with amniote embryos such as the chick, together with complementary data provided by genetic analyses of mouse and Drosophila development.

Animals↗

PubMed1990

The biological effects of XTC-MIF: quantitative comparison with Xenopus bFGF.

Mesoderm in Xenopus and other amphibian embryos is induced by signals from the vegetal hemisphere acting on equatorial or animal hemisphere cells. These signals are diffusible and two classes of candidate signal molecule have been identified: the fibroblast growth factor (FGF) and transforming growth factor beta (TGF-beta) types. In this paper, we compare the effects of cloned Xenopus basic FGF (XbFGF) and electophoretically homogeneous XTC-MIF (a TGF-beta-like factor obtained from a Xenopus cell line) on animal pole explants. We find that they have a similar minimum active concentration (0.1-0.2 ng ml-1) but that, nonetheless, XTC-MIF is at least 40 times more active in inducing muscle. In general, we find that the two factors cause inductions of significantly different characters in terms of tissue type, morphology, gene expression and timing. At low concentrations (0.1-1.0 ng ml-1) both factors induce the differentiation of 'mesenchyme' and 'mesothelium' as well as blood-like cells. These latter cells do not, however, react with an antibody to Xenopus globin. This raised the possibility that the identification of red blood cells in other studies on mesoderm induction might have been mistaken, but combinations of animal pole regions with ventral vegetal pole regions confirmed that genuine erythrocytes are formed. The identity of the blood-like cells formed in response to the inducing factors remains unknown. At higher concentrations XTC-MIF induces neural tissue, notochord, pronephros and substantial and often segmented muscle. By contrast, XbFGF only induces significant amounts of muscle above 24 ng ml-1 and even then this is much less than that induced by XTC-MIF. For both factors an exposure of less than 30 min is effective. Competence of animal pole cells to respond to XbFGF is completely lost by the beginning of gastrulation (stage 10) while competence to XTC-MIF is detectable until somewhat later (stage 11). Since animal pole tissue is known to be able to respond to the natural inducer at least until stage 10, and perhaps until stage 10.5, this suggests that bFGF cannot be the sole inducer of mesoderm in vivo. Taken together, these results are consistent with XTC-MIF being a dorsoanterior inducer and XbFGF a ventroposterior inducer, suggesting that body pattern is established by the interaction of two types of inducing signal. This model is discussed in view of the qualitative and quantitative differences between the factors.

Animals↗

PubMed1989

Inducing factors and the control of mesodermal pattern in Xenopus laevis.

The mesoderm of Xenopus laevis and other amphibia is formed through an inductive interaction during which cells of the vegetal hemisphere act on cells of the animal hemisphere. Two groups of factors mimic the effects of the vegetal hemisphere. One group consists of members of the fibroblast growth factor (FGF) family, while the other is related to transforming growth factor type beta (TGF-beta). In this paper we discuss the evidence that the FGF family represents 'ventral' mesoderm-inducing signals, and the TGF-beta family 'dorsal' signals. The evidence includes a discussion of the cell types formed in response to each type of factor, the fact that only XTC-MIF (a member of the TGF-beta family) and not bFGF can induce animal pole ectoderm to become Spemann's organizer, and an analysis of the timing of the gastrulation movements induced by the factors.

Animals↗

PubMed1988

On the specificity and effects on transcription of P-element insertions at the yellow locus of Drosophila melanogaster.

Fourteen P-element insertion mutants at the yellow (y) gene of D. melanogaster have been analysed by restriction mapping and DNA sequencing. The distribution of the insertion sites is nonrandom, with a preferred target site in the 5'-transcribed but non-translated leader of the gene. Transcription analysis indicates that P-elements inserted into the transcribed region of y can terminate y transcription. While the great majority of the P-element insertions into the preferred target site abolish y activity, this loss of activity is not due to disruption of the insertion site since imprecise excision events which do not restore the wild type sequence at the insertion site can restore y function. We further demonstrate that a mutant caused by a 221bp P-element insertion into the 5' transcribed but non-translated region, which show partial y activity, produces a larger mutant transcript consistent with it being a product of transcriptional readthrough. We present results which suggest that imprecise excision events which restore (or partially restore) y activity can occur by deleting P-element internal sequences which normally act to terminate y transcription.

Animals↗