Patterning the endoderm: the importance of neighbours

The endodermal germ layer gives rise to the inner epithelial lining of the gastrointestinal tract, while that of the mesoderm gives rise to the outer smooth muscle layer. Much of the work in chick shows that the mesoderm plays an important role in endodermal differentiation, and recent results in Xenopus have begun to elucidate the factors involved in establishing endodermal cell fate. However, little is know about the signals responsible for the initial specification and pattern of the endoderm. In a recent paper, Wells and Melton have investigated the importance of early mesectodermal-endodermal interactions in the initial specification of the early mouse endoderm.(1) They demonstrate that the initial specification and differentiation of the endoderm does not occur cell-autonomously, but requires signals released from the mesectoderm.     

A labile period in the determination of the anterior-posterior axis during early neural development in Xenopus.

The process by which the vertebrate central nervous system acquires its regional properties remains a central problem in developmental biology. It is generally argued that at early gastrula stages the dorsal mesoderm possesses precise anterior-posterior positional information, which is subsequently imparted to the overlying ectoderm. However, using regionally specific gene probes to monitor regional responses in Xenopus embryos, we find that anterior-posterior properties are not fixed until early neurula stages. During gastrulation the regional inducing capacities of the dorsal mesoderm as well as the regional responses of the presumptive neural ectoderm are activated along the entire anterior-posterior axis when these properties are assayed in recombinant and explant experiments, respectively. Restriction of regional inducing capacity in the mesoderm and responsiveness in the neural ectoderm occur only at neural plate stages.     

Determination and development of the larval muscle pattern in Drosophila melanogaster

This review describes briefly what is known about the early steps of mesoderm differentiation in the fruitfly Drosophila melanogaster. After a summary of general aspects including mesoderm differentiation, mesoderm cell migration and subdivision of the mesoderm, more detail is given about the specification of muscle progenitor cells, due to their role as the earliest obvious landmarks in muscle fiber development in Drosophila. Particular focus is given to recent results on the role of asymmetric cell division in muscle differentiation. Furthermore a short summary of myoblast fusion is provided.     

Endoderm specification and differentiation in Xenopus embryos

It is known from work with amniote embryos that regional specification of the gut requires cell-cell signalling between the mesoderm and the endoderm. In recent years, much of the interest in Xenopus endoderm development has focused on events that occur before gastrulation and this work has led to a different model whereby regional specification of the endoderm is autonomous. In this paper, we examine the specification and differentiation of the endoderm in Xenopus using neurula and tail-bud-stage embryos and we show that the current hypothesis of stable autonomous regional specification is not correct. When the endoderm is isolated alone from neurula and tail bud stages, it remains fully viable but will not express markers of regional specification or differentiation. If mesoderm is present, regional markers are expressed. If recombinations are made between mesoderm and endoderm, then the endodermal markers expressed have the regional character of the mesoderm. Previous results with vegetal explants had shown that endodermal differentiation occurs cell-autonomously, in the absence of mesoderm. We have repeated these experiments and have found that the explants do in fact show some expression of mesoderm markers associated with lateral plate derivatives. We believe that the formation of mesoderm cells by the vegetal explants accounts for the apparent autonomous development of the endoderm. Since the fate map of the Xenopus gut shows that the mesoderm and endoderm of each level do not come together until tail bud stages, we conclude that stable regional specification of the endoderm must occur quite late, and as a result of inductive signals from the mesoderm.     

Is mechano‐sensitive expression of twist involved In mesoderm formation?

Mesoderm invagination, the first morphogenetic movement of gastrulation in the early Drososphila embryo, is controlled by the expression of the twist and snail genes. Our knowledge concerning epistatic relationships between these genes implies the existence of a poorly understood biochemical maintenance of twist expression during mesoderm invagination by the snail gene. In the light of a review detailing the role of these genes in the cell shape changes leading to invagination, and of recent findings showing the expression of twist as mechanically sensitive, we suggest that the expression of twist in the mesoderm could alternatively be maintained by mechanical strains developed during mesoderm invagination.     

Transferrin and iron requirements of embryonic mesoderm cells cultured in hydrated collagen matrices

Summary Very early embryonic mesoderm cells were taken from the primitive streak-stage chick embryo and cultured in a matrix of type I collagen in the presence of serum. Previous work has shown that under these conditions cells do not leave the explant and move in the collagen in the absence of supplemented avian transferrin. Cells explanted onto tissue culture plastic in the presence of serum do not require this transferrin supplement. These observations were investigated further by culturing cells in collagen in the presence of the lipophilic iron chelator, ferric pyridoxal isonicotinoyl hydrazone (FePIH), which can replace transferrin as an iron-delivery agent. Under conditions in which FePIH could effectively stimulate chick embryo myoblast growth, no such long-term stimulation was obtained with the early mesoderm cells in collagen. This suggested that for mesoderm cells, FePIH could not replace transferrin. Antibody to the transferrin receptor and to transferrin itself inhibited growth of myoblasts in collagen and on plastic, and of mesoderm cells in collagen. Mesoderm cells on plastic, however, were refractory to the presence of the antibody directed to the receptor and seemed to show a low dependency on transferrin-delivered iron under these conditions, inasmuch as antiserum to transferrin itself only caused a partial inhibition of outgrowth. The results suggest that mesoderm cells in collagen require transferrin for both iron uptake and for another unspecified function. It is consistent with the results to propose that transferrin binding might modulate the cells' attachment to collagen, thus influencing outgrowth. The distribution of the actin cytoskeleton in mesoderm cells actively migrating in collagen, such as in the presence of transferrin, suggests a stronger attachment to the collagen than nonmigrating cells. This work was supported by an operating grant from the Medical Research Council of Canada.     

Mesodermal control of neural cell identity in vertebrates.

It has long been appreciated that the differentiation and patterning of neural cells is controlled in part by inductive signals from the mesoderm. Several recent experiments have revealed that distinct mesodermal signals act throughout early neural development and have begun to address the nature and sources of such signals.     

Mesoderm induction and erythroid differentiation in early vertebrate development

Little is known about the origin of hematopoietic cells in mammalian development. Here we view the problem in terms of the induction and patterning of the mesoderm, using Xenopus embryos as a model. In amphibia, mesoderm arises through an inductive interaction in which cells of the vegetal hemisphere act on overlying equatorial cells. Activin and FGF are two candidates for the mesoderm-inducing signal, with recent work showing that these factors are necessary for formation of different regions of the mesoderm and that different concentrations of factors induce different cell types. We discuss to what extent these observations apply to mammals.     

Effects of heterodimerization and proteolytic processing on Derrière and Nodal activity: implications for mesoderm induction in Xenopus

Derrière is a recently discovered member of the TGFbeta superfamily that can induce mesoderm in explant assays and is expressed at the right time and location to mediate mesoderm induction in response to VegT during Xenopus embryogenesis. We show that the ability of Derrière to induce dorsal or ventral mesoderm depends strictly on the location of expression and that a dominant-negative Derrière cleavage mutant completely blocks all mesoderm formation when ectopically expressed. This differs from the activity of similar Xnr2 cleavage mutant constructs, which are secreted and retain signaling activity. Additional analysis of mesoderm induction by Derrière and members of the Nodal family indicates that these molecules are involved in a mutual positive-feedback loop and antagonism of either one of the signals can reduce the other. Interaction between Derrière and members of the Nodal family is also shown to occur through the formation of heterodimeric ligands. Using an oocyte expression system we show direct interaction between the mature Derrière ligand and members of both the Nodal and BMP families. Taken together, these findings indicate that Derrière and Nodal proteins probably work cooperatively to induce mesoderm throughout the marginal zone during early Xenopus development.     

Crosstalk between the phosphatidylinositol cycle and MAP kinase signaling pathways in Xenopus mesoderm induction

Recent studies have established a role for the phosphoinositide (PI) cycle in the early patterning of Xenopus mesoderm. In explants, stimulation of this pathway in the absence of growth factors does not induce mesoderm, but when accompanied by growth factor treatment, simultaneous PI cycle stimulation results in profound morphological and molecular changes in the mesoderm induced by the growth factor. This suggests the possibility that the PI cycle exerts its influence via crosstalk, by modulating some primary mesoderm-inducing pathway. Given recent identification of mitogen-activated protein kinase (MAPK) as an intracellular mediator of some mesoderm-inducing signals, the present study explores MAPK as a potential site of PI cycle-mediated crosstalk .We report that MAPK activity, like PI cycle activity, increases in intact embryos during mesoderm induction. Phosphoinositide cycle stimulation during treatment of explants with basic fibroblast growth factor (bFGF) synergistically increases late-phase MAPK activity and potentiates bFGF-induced expression of Xbra , a MAPK-dependent mesodermal marker.     

Electrophysiological evidence for low-resistance intercellular junctions in the early chick embryo

Electrophysiological evidence is presented for the exchange of small ions directly between cells interiors, i.e. "electrical coupling," in the early chick embryo. Experiments with intracellular marking show that coupling is widespread, occurring between cells in the same tissue, e.g. ectoderm, notochord, neural plate, mesoderm, and Hensen's node, and between cells in different tissues, e.g. notochord to neural plate, notochord to neural tube, notochord to mesoderm. The coupling demonstrates the presence of specialized low-resistance intercellular junctions as found in other embryos and numerous adult tissues. The results are discussed in relation to recent electron microscopical studies of intercellular junctions in the early chick embryo. The function of the electrical coupling in embryogenesis remains unknown, but some possibilities are considered.     

Researches on the formation of axial organs in the chick embryo. X. Further investigations on the role of ecto- and endoderm in somitogenesis

In continuation of previous experiments, recent results concerning the determinism of somitogenesis are reported. By means of two experimental devices on explanted chick embryos the influence upon mesoderm segmentation of the early removal of ectoderm (neural plate)--before and during the formation of the first somite pairs--and removal of endo- and ectoderm after 36-40 hours of incubation was investigated. Up to date results attest that during the shaping of the first somites no essential epigenetic interrelations between overlying ectoderm (neural plate) and paraxial mesoderm are necessary for segmentation. Just before the onset of segmentation a labile determination seems to be present in the presumptive somitogenic mesoderm. As to the later role of endo- and ectoderm in segmentation, present results reveal a relative independence of the segmentation process. The absence of the above-mentioned layers does not prevent further segmentation but induces a progressive slowing down of the process.     

Timed interactions between the Hox expressing non-organiser mesoderm and the Spemann organiser generate positional information during vertebrate gastrulation

We report a novel developmental mechanism. Anterior-posterior positional information for the vertebrate trunk is generated by sequential interactions between a timer in the early non-organiser mesoderm and the organiser. The timer is characterised by temporally colinear activation of a series of Hox genes in the early ventral and lateral mesoderm (i.e., the non-organiser mesoderm) of the Xenopus gastrula. This early Hox gene expression is transient, unless it is stabilised by signals from the Spemann organiser. The non-organiser mesoderm and the Spemann organiser undergo timed interactions during gastrulation which lead to the formation of an anterior-posterior axis and stable Hox gene expression. When separated from each other, neither non-organiser mesoderm nor the Spemann organiser is able to induce anterior-posterior pattern formation of the trunk. We present a model describing that convergence and extension continually bring new cells from the non-organiser mesoderm within the range of organiser signals and thereby create patterned axial structures. In doing so, the age of the non-organiser mesoderm, but not the age of the organiser, defines positional values along the anterior-posterior axis. We postulate that the temporal information from the non-organiser mesoderm is linked to mesodermal Hox expression.     

Regulation of trunk myogenesis by the neural crest: a new facet of neural crest-somite interactions

It is well established that the somitic mesoderm regulates early stages of neural crest development and further segmentation of crest-derived peripheral ganglia. The possibility that neural crest progenitors feed back on the somites was, however, not explored. Two recent studies provide evidence that the neural crest regulates somite-derived myogenesis by distinct mechanisms.