Mesoderm-inducing factors and the control of gastrulation

Development ◽  
1992 ◽  
Vol 116 (Supplement) ◽  
pp. 127-136 ◽  
Author(s):  
J. C. Smith ◽  
J. E. Howard

One of the reasons that we know so little about the control of vertebrate gastrulation is that there are very few systems available in which the process can be studied in vitro. In this paper, we suggest that one suitable system might be provided by the use of mesoderm-inducing factors. In amphibian embryos such as Xenopus laevis, gastrulation is driven by cells of the mesoderm, and the mesoderm itself arises through an inductive interaction in which cells of the vegetal hemisphere of the embryo emit a signal which acts on overlying equatorial cells. Several factors have recently been discovered that modify the pattern of mesodermal differentiation or induce mesoderm from presumptive ectoderm. Some of these mesoderm-inducing factors will also elicit gastrulation movements, which provides a powerful model system for the study of gastrulation, because a population of cells that would not normally undertake the process can be induced to do so. In this paper, we use mesoderm-inducing factors to attempt to answer four questions. How do cells know when to gastrulate? How do cells know what kind of gastrulation movement to undertake? What is the cellular basis of gastrulation? What is the molecular basis of gastrulation?

Development ◽  
1989 ◽  
Vol 107 (Supplement) ◽  
pp. 149-159 ◽  
Author(s):  
J. C. Smith ◽  
J. Cooke ◽  
J. B. A. Green ◽  
G. Howes ◽  
K. Symes

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 typeβ(TGF-β). In this paper we discuss the evidence that the FGF family represents ‘ventral’ mesoderm-inducing signals, and the TGF-β family ‘dorsal’ signals. The evidence includes a discussion of the cell types formed in response to each type of factor, the fact that only XTCMIF (a member of the TGF-β 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.


1998 ◽  
Vol 76 (6) ◽  
pp. 947-956 ◽  
Author(s):  
Kyunghee Choi

Hematopoietic and endothelial cell lineages are the first to mature from mesoderm in the developing embryo. However, little is known about the molecular and (or) cellular events leading to hematopoietic commitment. The recent applications of technology utilizing gene targeted mice and the employment of many available in vitro systems have facilitated our understanding of hematopoietic establishment in the developing embryo. It is becoming clear that embryonic hematopoiesis occurs both in the extra-embryonic yolk sac and within the embryo proper in the mouse. The existence of the long pursued hemangioblast, a common progenitor of hematopoietic and endothelial cells, is now formally demonstrated. Based on this new information, many studies are being conducted to understand hematopoietic commitment events from mesoderm. In this review, we will first discuss the establishment of the hematopoietic system with special emphasis on the most primitive hematopoietic committed cells, the hemangioblast. We will then discuss mesoderm-inducing factors and their possible role in hematopoietic lineage commitment.Key words: hematopoietic commitment, hemangioblast, in vitro embryonic stem cell differentiation.


Development ◽  
1987 ◽  
Vol 101 (2) ◽  
pp. 339-349 ◽  
Author(s):  
K. Symes ◽  
J.C. Smith

The first inductive interaction in amphibian development is mesoderm induction, in which an equatorial mesodermal rudiment is induced from the animal hemisphere under the influence of a signal from vegetal pole blastomeres. We have recently discovered that the Xenopus XTC cell line secretes a factor which has the properties we would expect of a mesoderm-inducing factor. In this paper, we show that an early response to this factor by isolated Xenopus animal pole regions is a change in shape, involving elongation and constriction. We show by several criteria, including general appearance, timing, rate of elongation and the nonrequirement for cell division that these movements resemble the events of gastrulation. We also demonstrate that the movements provide an early, simple and reliable indicator of mesoderm induction and are of use in providing a ‘model system’ for the study of mesoderm induction and gastrulation. For example, we show that the timing of gastrulation movements does not depend upon the time of receipt of a mesoderm-induction signal, but on an intrinsic gastrulation ‘clock’ which is present even in those animal pole cells that would not nomally require it.


Author(s):  
Darcy B. Kelley ◽  
Martha L. Tobias ◽  
Mark Ellisman

Brain and muscle are sexually differentiated tissues in which masculinization is controlled by the secretion of androgens from the testes. Sensitivity to androgen is conferred by the expression of an intracellular protein, the androgen receptor. A central problem of sexual differentiation is thus to understand the cellular and molecular basis of androgen action. We do not understand how hormone occupancy of a receptor translates into an alteration in the developmental program of the target cell. Our studies on sexual differentiation of brain and muscle in Xenopus laevis are designed to explore the molecular basis of androgen induced sexual differentiation by examining how this hormone controls the masculinization of brain and muscle targets.Our approach to this problem has focused on a highly androgen sensitive, sexually dimorphic neuromuscular system: laryngeal muscles and motor neurons of the clawed frog, Xenopus laevis. We have been studying sex differences at a synapse, the laryngeal neuromuscular junction, which mediates sexually dimorphic vocal behavior in Xenopus laevis frogs.


2020 ◽  
Author(s):  
Sean A. Newmister ◽  
Kinshuk Raj Srivastava ◽  
Rosa V. Espinoza ◽  
Kersti Caddell Haatveit ◽  
Yogan Khatri ◽  
...  

Biocatalysis offers an expanding and powerful strategy to construct and diversify complex molecules by C-H bond functionalization. Due to their high selectivity, enzymes have become an essential tool for C-H bond functionalization and offer complementary reactivity to small-molecule catalysts. Hemoproteins, particularly cytochromes P450, have proven effective for selective oxidation of unactivated C-H bonds. Previously, we reported the in vitro characterization of an oxidative tailoring cascade in which TamI, a multifunctional P450 functions co-dependently with the TamL flavoprotein to catalyze regio- and stereoselective hydroxylations and epoxidation to yield tirandamycin A and tirandamycin B. TamI follows a defined order including 1) C10 hydroxylation, 2) C11/C12 epoxidation, and 3) C18 hydroxylation. Here we present a structural, biochemical, and computational investigation of TamI to understand the molecular basis of its substrate binding, diverse reactivity, and specific reaction sequence. The crystal structure of TamI in complex with tirandamycin C together with molecular dynamics simulations and targeted mutagenesis suggest that hydrophobic interactions with the polyene chain of its natural substrate are critical for molecular recognition. QM/MM calculations and molecular dynamics simulations of TamI with variant substrates provided detailed information on the molecular basis of sequential reactivity, and pattern of regio- and stereo-selectivity in catalyzing the three-step oxidative cascade.<br>


1996 ◽  
Vol 271 (43) ◽  
pp. 27188
Author(s):  
Lloyd W. Ruddock ◽  
Jeremy J.F. Coen ◽  
Caroline Cheesman ◽  
Robert B. Freedman ◽  
Timothy R. Hirst

2000 ◽  
Vol 31 (3) ◽  
pp. 499-509 ◽  
Author(s):  
Joel S. Greenberger ◽  
Julie P. Goff ◽  
Jason Bush ◽  
Alfred Bahnson ◽  
Douglas Koebler ◽  
...  

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