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PubMedDate not supplied

dpp induces mesodermal gene expression in Drosophila.

Inductive interactions between germ layers are an essential feature of the development of many organisms. In several species these interactions are mediated by members of the transforming growth factor-beta (TGF beta) family. In amphibians, different concentrations of activin can induce different types of mesoderm in the animal cap assay. In Drosophila, a member of the TGF beta family, decapentaplegic (dpp), acts as an inductive signal. Midway through embryogenesis, dpp is expressed in the visceral mesoderm, and enhances the expression of the homeotic gene labial in the underlying midgut endoderm. Earlier in development, however, dpp expression is limited to the dorsal ectoderm. At this stage in development, thickveins, a dpp receptor, is expressed in the mesoderm, and this suggests that ectodermal dpp might not only be required for development of dorsal ectoderm, but could also act inductively to mediate pattern formation in the underlying mesoderm. Here we show, by expressing dpp ectopically in the ectoderm and mesoderm and by examining dpp null mutant embryos, that dpp regulates expression of mesodermal genes.

Animals↗
PubMed1998

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.

Animals↗
PubMed2002

Signals that instruct somite and myotome formation persist in Xenopus laevis early tailbud stage embryos.

Somite formation is a lengthy process that begins at gastrulation and continues through tailbud stages to form approximately 50 pairs of somites in the frog, Xenopus laevis. In Xenopus, the somite primarily gives rise to myotome. We sought to determine whether the formation of somites and myotome requires a transient signal active during gastrulation or a constitutive signal active throughout development to instruct dorsal mesodermal cells to form the posterior somites. Previous work from our lab revealed that cells from the neural ectoderm are capable of responding to mesoderm-inducing signals [Domingo and Keller: Dev Biol 2000;225:226-240]. Thus, to test for the presence of somite-inducing signals, we performed a series of grafting experiments in which we used gastrula cells from the anterior neural ectoderm (ANE). Fluorescently labeled ANE cells were grafted to the posterior paraxial mesoderm of progressively older host embryos between stages 11 (mid gastrula) and 23 (early tailbud). Our results showed that signals within the paraxial mesoderm can instruct prospective ANE cells, which normally give rise to head structures, to instead differentiate into myotome cells. We found that the grafted cells adopted the local paraxial mesoderm cell behaviors, which consists of mediolateral intercalation, segmentation, somite cell rotation, and differentiation to myotome. In addition, we show that the grafted ANE cells that adopt a myotome morphology also express the muscle-specific marker, 12/101. Through a series of heterochronic grafts, we determined that the duration of somite-inducing signals extends from the early gastrula (stage 11) through the early tailbud (stage 23) stage embryos. These results demonstrate that somite induction is not a transient event that occurs during gastrulation, but that it is instead a continuous event that can occur as new somites are added to the posterior axis.

Animals↗
PubMed2003

Noradrenergic neurons in the zebrafish hindbrain are induced by retinoic acid and require tfap2a for expression of the neurotransmitter phenotype.

Tfap2a is a transcriptional activator expressed in many different cell types, including neurons, neural crest derivatives and epidermis. We show that mutations at the zebrafish locus previously called mont blanc (mob) or lockjaw (low) encode tfap2a. The mutant phenotype reveals that tfap2a is essential for the development of hindbrain noradrenergic (NA) neurons of the locus coeruleus, medulla and area postrema, as well as for sympathetic NA neurons, epibranchial placode derived visceral sensory ganglia, and craniofacial and trunk crest derivatives. We focus our analysis on the role of tfap2a NA differentiation in the CNS. In the locus coeruleus, Phox2a and Tfap2a are co-expressed and are both required for NA development. By contrast, in the medulla Phox2a and Tfap2a are expressed in adjacent overlapping domains, but only tfap2a activity is required for NA differentiation, as NA neurons develop normally in soulless/phox2a mutant medulla. phox2a and tfap2a do not appear to affect each others expression. Our studies show that two distinct inductive mechanisms control NA development in the zebrafish hindbrain. For the posterior hindbrain, we identify retinoic acid as an important signal to induce NA differentiation in the medulla oblongata and area postrema, where it expands the tfap2a expression domain and thus acts upstream of tfap2a. By contrast, previous work revealed Fgf8 to be involved in specification of NA neurons in the locus coeruleus. Thus, although the inductive signals may be distinct, hindbrain NA neurons of the locus coeruleus and the posterior groups both require Tfap2a to establish their noradrenergic identity.

Adrenergic alpha-Agonists↗
PubMed2001

Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R asymmetry by the mouse node.

Genetic analyses in Drosophila have demonstrated that the multipass membrane protein Smoothened (Smo) is essential for all Hedgehog signaling. We show that Smo acts epistatic to Ptc1 to mediate Shh and Ihh signaling in the early mouse embryo. Smo and Shh/Ihh compound mutants have identical phenotypes: embryos fail to turn, arresting at somite stages with a small, linear heart tube, an open gut and cyclopia. The absence of visible left/right (L/R) asymmetry led us to examine the pathways controlling L/R situs. We present evidence consistent with a model in which Hedgehog signaling within the node is required for activation of Gdf1, and induction of left-side determinants. Further, we demonstrate an absolute requirement for Hedgehog signaling in sclerotomal development and a role in cardiac morphogenesis.[Dedicated to Rosa Beddington, a pioneer in mammalian embryology].

Animals↗
PubMed1996

Endoderm induction by the organizer-secreted factors chordin and noggin in Xenopus animal caps.

Spemann's organizer has potent neural inducing and mesoderm dorsalizing activities in the Xenopus gastrula. A third activity, the organizer's ability to induce a secondary gut, has been difficult to analyze experimentally due to the lack of early gene markers. Here we introduce endodermin, a pan-endodermal gene marker, and use it to demonstrate that chordin (Chd), a protein secreted by the organizer region, is able to induce endodermal differentiation in Xenopus. The ability of chd, as well as that of noggin, to induce endoderm in animal cap explants is repressed by the ventralizing factor BMP-4. When FGF signaling is blocked by a dominant-negative FGF receptor in chd-injected animal caps, neural induction is inhibited and most of the explant is induced to become endoderm. The results suggest that proteins secreted by the organizer, acting together with known peptide growth factors, regulate differentiation of the endodermal germ layer.

Amino Acid Sequence↗
PubMed1992

Changes in dorsoventral but not rostrocaudal regionalization of the chick neural tube in the absence of cranial notochord, as revealed by expression of engrailed-2.

Notochord has been implicated in previous studies in both the dorsoventral and rostrocaudal patterning of the developing neural tube. This possibility has been further explored by analyzing the expression of Engrailed-2 in chick embryos developing with cranial notochord defects. Control embryos containing intact notochords expressed Engrailed-2 protein within the neural tube and in a subset of the neural crest and overlying surface ectoderm at the future mesencephalon and cranial metencephalon levels. Within the neural tube, expression was confined to cell nuclei in the roof plate and lateral walls; floor plate nuclei directly overlying the notochord typically failed to show expression. After surgical removal of Hensen's node, the source of notochord precursor cells, embryos were cultured through neurulation and assayed for expression of Engrailed-2 protein. All embryos that partially or completely lacked cranial notochord expressed Engrailed-2 in a pattern similar to that of control embryos containing intact notochords, except that when notochord and floor plate were absent, Engrailed-2 was also expressed in the most ventral part of the neural tube. These results indicate that 1) Engrailed-2 expression is suppressed in the most ventral neural tube owing to induction of the floor plate by the notochord, and 2) that the presence of an underlying notochord is not required for correct rostrocaudal expression, suggesting that multiple pathways act in the patterning of the rudiment of the central nervous system.

Animals↗
PubMed1995

Protein kinase A and hedgehog signaling in Drosophila limb development.

The Drosophila hedgehog (hh) gene encodes a secreted protein involved in organizing growth and patterning in many developmental processes. Hh appears to act by inducing the localized expression of at least two other signaling molecules, decapentaplegic (dpp) and wingless (wg), which then govern cell proliferation and patterning in surrounding tissue. Here, we demonstrate that cyclic AMP (cAMP)-dependent protein kinase A (PKA) is essential during limb development to prevent inappropriate dpp and wg expression. We also show that a constitutively active form of PKA can prevent inappropriate dpp and wg expression, but does not interfere with their normal induction by hh. We propose that the basal activity of PKA imposes a block on the transcription of dpp and wg and that hh exerts its organizing influence by alleviating this block.

Animals↗
PubMed1999

A novel guanine exchange factor increases the competence of early ectoderm to respond to neural induction.

Inductive interactions between different cell layers have an extremely important role in early embryogenesis. One of the most intensively studied and best characterised of these is the induction of neural tissue from ectodermal cells by the dorsal mesoderm. The competence of ectodermal cells to respond to neural induction varies according to dorsal-ventral position; with dorsal ectoderm (much of which forms the neural plate) having a far higher competence. Here we show that overexpression of the nucleotide exchange factor lfc increases ectodermal competence for neural induction as well as the amount of neural tissue in the whole embryo. Lfc is expressed pan ectodermally soon after gastrulation and may respond to an early determinant of dorsal ectoderm.

Animals↗
PubMed1997

Early steps in vertebrate cardiogenesis.

Heart formation provides an excellent model for studying the molecular basis of cell determination in vertebrate embryos. By combining molecular assays with the experimental approaches of classic embryology, a model for the cell signalling events that initiate cardiogenesis is emerging. Studies of chick, amphibian, and fish embryos demonstrate the inductive role of dorso-anterior endoderm in specifying the cardiac fate of adjacent mesoderm. A consequence of this signalling is the onset of cardiomyogenesis and several transcription factors--Nkx2-5-related, HAND, GATA and MEF-2 families--contribute to these events.

Amphibians↗
PubMed1995

Developmental control point in induction of thymic cortex regulated by a subpopulation of prothymocytes.

T lymphocytes of the alpha/beta T-cell receptor (TCR) lineage mature in the thymus, where they undergo a series of differentiation, expansion and selection events. For normal T-cell ontogeny to occur, thymocytes must interact physically with cortical and medullary thymic stroma cells. In parallel, interactions of the thymic stromal cells with TCR-positive thymocytes are necessary for the development of the thymic medulla. Comparable requirements for the differentiation of the cortex have not been defined, however. Here we analyse mutant mouse strains to assess the function of early prothymocytes in the induction of the thymic cortex. We find that animals with a developmental block at the earliest stage of T-lineage commitment lack a functional thymic cortex. This abnormality could be corrected in fetal but not adult animals by transplantation of either fetal or adult wild-type haematopoietic stem cells. Thus a developmentally restricted interaction of fetal stromal cells with early prothymocytes is required for the induction of a cortical microenvironment. In addition, a normal thymic architecture is necessary for sustained T-cell ontogeny.

Aging↗
PubMed2004

The T-box transcription factors TBX-37 and TBX-38 link GLP-1/Notch signaling to mesoderm induction in C. elegans embryos.

The four-cell C. elegans embryo contains two sister cells called ABa and ABp that initially have equivalent abilities to produce ectodermal cell types. Multiple Notch-mediated interactions occur during the early cell divisions that diversify the ABa and ABp descendants. The first interaction determines the pattern of ectodermal cell types produced by ABp. The second interaction induces two ABa granddaughters to become mesodermal precursors. We show that T-box transcription factors called TBX-37 and TBX-38 are essential for mesodermal induction, and that these factors are expressed in ABa, but not ABp, descendants. We provide evidence that the first Notch interaction functions largely, if not entirely, to prevent TBX-37, TBX-38 expression in ABp descendants. Neither the second Notch interaction nor TBX-37, TBX-38 alone are sufficient for mesodermal induction, indicating that both must function together. We conclude that TBX-37, TBX-38 play a key role in distinguishing the outcomes of two sequential Notch-mediated interactions.

Amino Acid Sequence↗
PubMed1989

The localization of an inductive response.

Combinations of tissues from Xenopus blastulae have been used to identify several mechanisms that limit the number of animal cells forming muscle after induction by vegetal cells. The results disagree with a model in which direct physical contact or very close proximity between animal and vegetal cells restricts the number of cells that receive the inductive signal. Rather it seems that a diffusible inducer is released by vegetal cells, and spreads through 4-8 animal cell diameters, equivalent to a distance of 80 microns, from the nearest vegetal cells. Several factors seem to cooperate to prevent the further spread of the mesoderm-forming induction. These include the slow diffusion and/or instability of the inducer, the time of loss of competence of animal cells to respond to induction, and the amount of vegetal tissue that releases inducer for a limited time. The combination of these, and perhaps other, processes seems to ensure that a consistent minority of animal cells are induced to form muscle, thereby leaving other animal cells available to form the nervous system and epidermis.

Animals↗
PubMed1997

Expression of Pax-3 is initiated in the early neural plate by posteriorizing signals produced by the organizer and by posterior non-axial mesoderm.

Pax-3 is a paired-type homeobox gene that is specifically expressed in the dorsal and posterior neural tube. We have investigated inductive interactions that initiate Pax-3 transcript expression in the early neural plate. We present several lines of evidence that support a model where Pax-3 expression is initiated by signals that posteriorize the neuraxis, and then secondarily restricted dorsally in response to dorsal-ventral patterning signals. First, in chick and Xenopus gastrulae the onset of Pax-3 expression occurs in regions fated to become posterior CNS. Second, Hensen's node and posterior non-axial mesoderm which underlies the neural plate induce Pax-3 expression when combined with presumptive anterior neural plate explants. In contrast, presumptive anterior neural plate explants are not competent to express Pax-3 in response to dorsalizing signals from epidermal-ectoderm. Third, in a heterospecies explant recombinant assay with Xenopus animal caps (ectoderm) as a responding tissue, late, but not early, Hensen's node induces Pax-3 expression. Chick posterior non-axial mesoderm also induces Pax-3, provided that the animal caps are neuralized by treatment with noggin. Finally we show that the putative posteriorizing factors, retinoic acid and bFGF, induce Pax-3 in neuralized animal caps. However, blocking experiments with a dominant-inhibitory FGF receptor and a dominant-inhibitory retinoic acid receptor suggest that Pax-3 inductive activities arising from Hensen's node and posterior non-axial mesoderm do not strictly depend on FGF or retinoic acid.

Animals↗
PubMed1993

[Regionalization of the expression of tenascin as a response to the inducers of mesoderm].

Tenascin (TN) is an extracellular matrix (ECM) glycoprotein which possesses antiadhesive properties and thus is able to modulate cell interactions with molecules of the ECM. In Xenopus embryos, TN is expressed dorsally in a very restricted pattern. We have studied the distribution of TN mRNA in tailbud-stage embryos by in situ hybridization. We show that TN transcripts are principally expressed in myotome cells. No TN mRNA could be detected in lateral plate mesoderm. This had led us to study TN expression in response to mesodermal inducers. Analysis of the distribution of TN after mesodermal induction of blastula animal caps with activin A and bFGF or after ectopic expression of XBra shows that TN expression is elicited when dorsal or posterior structures are formed. Our results show that TN regionalization in Xenopus embryos depends on mesoderm patterning.

Activins↗
PubMed1984

Avian scale development. X. Dermal induction of tissue-specific keratins in extraembryonic ectoderm.

Epidermal-dermal tissue interactions regulate morphogenesis and tissue-specific keratinization of avian skin appendages. The morphogenesis of scutate scales differs from that of reticulate scales, and the keratin polypeptides of their epidermal surfaces are also different. Do the inductive cues which initiate morphogenesis of these scales also establish the tissue-specific keratin patterns of the epidermis, or does the control of tissue-specific keratinization occur at later stages of development? Unlike feathers, scutate and reticulate scales can be easily separated into their epidermal and dermal components late in development when the major events of morphogenesis have been completed and keratinization will begin. Using a common responding tissue (chorionic epithelium) in combination with scutate and reticulate scale dermises, we find that these embryonic dermises, which have completed morphogeneis, can direct tissue-specific stratification and keratinization. In other words, once a scale dermis has acquired its form, through normal morphogenesis, it is no longer able to initiate morphogenesis of that scale, but it can direct tissue-specific stratification and keratinization of a foreign ectodermal epithelium, which itself has not undergone scale morphogenesis.

Animals↗
PubMed1988

Close juxtaposition between inducing chordamesoderm and reacting neuroectoderm is a prerequisite for neural induction in Xenopus laevis.

The results of this study indicate that the induction of the central nervous system in Xenopus laevis depends on the close juxtaposition of inducing chordamesoderm and reacting ectoderm, which is necessary for the short distance migration of neural inducing factors. The examination of the neuroectoderm-chordamesoderm interface at intervals of 1 h up to 5 h showed that the onset of neural induction is correlated to the degree of contact formation between ectodermal and mesodermal cells. In the ectoderm cells the number of coated pits, a feature of receptor-mediated endocytosis, is increased. Furthermore there exist telophase bridges between some ectoderm cells, which are possibly correlated to secondary cell interactions.

Animals↗
PubMed2002

Smad10 is required for formation of the frog nervous system.

Before the nervous system establishes its complex array of cell types and connections, multipotent cells are instructed to adopt a neural fate and an anterior-posterior pattern is established. In this report, we show that Smad10, a member of the Smad family of intracellular transducers of TGFbeta signaling, is required for formation of the nervous system. In addition, two types of molecules proposed as key to neural induction and patterning, bone morphogenetic protein (BMP) antagonists and fibroblast growth factor (FGF), require Smad10 for these activities. These data suggest that Smad10 may be a central mediator of the development of the frog nervous system.

Animals↗