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Early development of macrophages in intact and organ cultured hearts of rat embryos.

BACKGROUND: Macrophage precursors are present early in embryonic life, being demonstrable in placental and embryonic connective tissues of rats at the neurula stage and as potential macrophages in the brain, liver, and lungs near the onset of organogenesis. We examined the development of macrophages in the heart and the possibility that they initially appear at sites of programmed cell death (apoptosis). METHODS: Precursors were recognized by the binding of peroxidase-coupled Griffonia simplicifolia isolectin B4 (GSA) on the cell membrane. Their capacity for conversion into macrophages was assayed in organ cultures; confirmation of the progeny as bona fide macrophages was obtained from their responses to particle exposure and macrophage colony-stimulating factor (M-CSF). RESULTS: GSA+cells were first seen on gestational day 12 (4 mm embryos) as 2-3 cycling, nonvacuolated cells located in cardiac tissue outside the blood vessels. This population increased to approximately 12 cells by day 14 (9 mm embryos). Two-thirds were distributed along the bulbus cordis in the jellylike endocardium and a more densely cellular connective tissue closer to the aortic arches where apoptotic sites are expected to develop. Such sites were not found in serial glycol methacrylate sections through our 14-day specimens, although in whole heart explants of this age an area of necrosis developed along the prospective line of bulbar endocardial fusion on the second day of organ culturing, and by then macrophages were fairly abundant. Organ culturing of 13-day embryonic hearts also yielded large, highly vacuolated, GSA+mononuclear phagocytes. After a few days in culture most of the macrophages migrated onto the medium where they formed a tight corona of cells about the explants. They readily ingested iron oxide particles and concentrated supravitally administered neutral red in their vacuoles. Macrophages from 14-day cultures exposed to M-CSF developed significantly larger coronas than macrophages from explants grown in serum-rich control medium (p < 0.001). In the presence of cytokines, moreover, these cardiac macrophages survived as many as 100 (92 "postnatal") days. CONCLUSIONS: Macrophage precursors first appear in embryonic rat hearts well before they are needed to clear debris generated by programmed cell death and are capable of rapid conversion into outright phagocytic cells as early as the 13th prenatal day.

Animals↗

Effects of oxygen toxicity on early development of mouse embryos.

To examine the effects of oxygen toxicity on embryonic development, mouse pronuclear embryos were cultured under low oxygen conditions with or without superoxide dismutase (SOD), and the blastulation rate was compared with that of embryos cultured under standard conditions. The blastulation rate of mouse pronuclear embryos cultured under standard conditions was only 1.5% (2/131). This rate was increased significantly, to 28.5% (43/151), when the embryos were cultured under low oxygen conditions; and to 31.0% (35/113) when SOD (500 micrograms/ml) was added to the medium under standard conditions; the rate was increased to 75.2% (115/153) when the embryos were cultured under low oxygen conditions in the presence of SOD. The minimum effective concentration of SOD in the culture medium was 50 micrograms/ml under conditions of 5% O2. The blastulation rate was significantly decreased after 1-hr exposure of pronuclear embryos to room atmospheric oxygen concentration (20% O2), and subsequent culture under 5% O2 with SOD did not result in an improved blastulation rate. Culture with SOD under 5% O2 promoted the development of two-cell stage embryos to the blastocyst stage. When two-cell stage embryos were collected 48 hr after hCG and cultured for 66 hr, their blastulation rate was similar to that of embryos collected from mice 114 hr after hCG. These results suggested that embryonic development in vitro is greatly affected by atmospheric oxygen throughout the early embryonic stages and that this harmful effect can be prevented by culturing embryos under low oxygen conditions and in the presence of SOD.

Animals↗

CDEBP, a site-specific DNA-binding protein of the 'APP-like' family, is required during the early development of the mouse.

A murine protein, termed CDEBP, was previously shown to bind the double-stranded DNA motif GTCACATG, identical to the yeast centromeric element CDEI. The cDNA sequence showed three domains with extensive similarities to the amyloid beta precursor protein (APP). The protein is homologous over its entire length to the human protein designated APPH. In situ immunofluorescence assays using antibodies raised against distinct parts of CDEBP detected discrete sites of accumulation inside the interphase nucleus, and the bulk of the protein was not associated with mitotic chromosomes. One of the complexes with double-stranded CDEI oligonucleotides detected by gel shift assay was not present when the protein had been selectively removed from nuclear extracts by immunoprecipitation. We reported previously that microinjection into one-cell mouse embryos of DNA fragments including the CDEI sequence results in an early arrest of development with abnormal nuclei containing variable amounts of DNA. The same characteristic figures were observed when embryos were treated with antisense oligonucleotides complementary to parts of the CDEBP coding region. Complexes between the CDEBP protein and CDEI sites in the mouse genome thus appear to play a critical role in the replication/segregation of the embryonic genome.

3T3 Cells↗

Parental imprinting on the mouse X chromosome: effects on the early development of X0, XXY and XXX embryos.

To examine the effects of X-chromosome imprinting during early mouse embryogenesis, we attempted to produce XM0, XP0, XMXMY, XMXPY and XMXMXP (where XM and XP stand for the maternally and the paternally derived X chromosome, respectively) making use of mouse strains bearing the translocation Rb(X.2)2Ad and the inversion In(X)1H. Unlike XMXPY embryos, XMXMY and XMXMXP conceptuses suffered from severe growth retardation or abnormal development characterized by deficient extra-embryonic structures at 6.5-7.5 days post coitum (dpc). A cytogenetic study suggested that two XM chromosomes remaining active in certain nonepiblast cells were responsible for the serious developmental abnormality found in these embryos disomic for XM. Although matings involving females heterozygous for Rb(X.2)Ad hinted at the paucity of XP0 embryos relative to those having the complementary karyotype of XMXMXP, further study of embryos from matings between females heterozygous for In(X)1H and Rb2Ad males did not substantiate this observation. Thus, the extensive peri-implantation loss of XP0 embryos shown by Hunt (1991) may be confined to X0 mothers. Taken together, this study failed to reveal a parentally imprinted X-linked gene essential for early mouse embryogenesis other than the one most probably corresponding to the X-chromosome inactivation centre.

Animals↗

Early development of serotonin neuron in the rat brain as studied by immunohistochemistry combined with tryptophan administration.

Early differentiation of serotonin (5HT) neurons was studied by an immunohistochemical technique in the metencephalon of rat embryos of CR lengths of 6 mm to 22 mm. Pregnant dams were treated with tryptophan (100 mg/kg) and pargyline (100 mg/kg). The synthesis of 5HT after tryptophan loading first occurs at any stage in the premature cells located in the ependymal layer. The cells appearing at the later embryonic stage begin 5HT synthesis at an earlier developmental stage of neurons with greater capacity to produce 5HT. Two different processes were revealed for the development of 5HT neurons. Most of the 5HT neuroblasts first give off axonal processes and then begin to migrate toward the mantle layer with reversed rotation. Some of the 5HT neuroblasts, later generated in the rostral pons in particular, display characteristic transformation without notable migration. After sending out of axonal processes ventrally, the apical processes are transformed into a number of dendritic processes directed toward the ventricular surface.

Animals↗

Synchronization of neuronal activity promotes survival of individual rat neocortical neurons in early development.

Neural activity is thought to play a significant role during the development of the cerebral cortex. In this study, we examined the effects of global activity block or enhancement and the effects of patterned firing on the ability of cultured rat neocortical neurons to survive during the second week in vitro, beyond the beginning of synaptogenesis. Blockade of neuronal activity by adding tetrodotoxin (TTX) and increasing magnesium concentration in the medium strongly reduced the survival of cortical cells. Increasing neuronal activity by raising the external potassium concentration significantly improved the survival of cortical neurons. We postulated that in a developing neuronal network the survival of nerve cells is regulated by synaptically mediated events that involve changes in the intracellular calcium concentration. To examine this question further, we monitored the activity of the developing network by optically recording the intracellular calcium signals of many neurons simultaneously. These recordings show that in low magnesium neocortical neurons express synchronized oscillation of their intracellular calcium concentration. The ability of a network to synchronize the changes in intracellular calcium of multiple cells appeared gradually during the second week in culture, paralleled by both an increase in the synaptic density and a decline in the number of surviving neurons. By examining the fate of identified cells several days after a recording session, we found that those nerve cells that were co-activated with other neurons had a significantly higher chance to survive than cells that did not participate in synchronized events. These experiments demonstrate that during early cortical network development cortical neurons show synchronized firing activity and that the survival of neurons is at least partially dependent on this pattern of neuronal activity.

Animals↗

Early development of functional spatial maps in the zebrafish olfactory bulb.

In the adult olfactory bulb (OB), particular chemical classes of odorants preferentially activate glomeruli within loosely defined regions, resulting in a coarse and fractured "chemotopic" map. In zebrafish, amino acids and bile acids predominantly stimulate glomeruli in the lateral and medial OB, respectively. We studied the development of these spatial response maps in zebrafish. At 3 d postfertilization (dpf), the OB contained protoglomerular structures that became refined and more numerous during subsequent days. In a transgenic zebrafish line expressing the Ca2+ indicator protein inverse pericam, mainly in mitral cells, odor responses in the OB were first detected at 2.5-3 dpf. Already at this stage, amino acids and bile acids evoked activity predominantly in the lateral and medial OB, respectively. Two-photon Ca2+ imaging using a synthetic indicator was used to reconstruct activity patterns at higher resolution in three dimensions. Responses to amino acids and bile acids were detected predominantly in the lateral and medial OB, respectively, with little overlap. Between 2.5 and 6 dpf, the number of odor-responsive units increased, but the overall spatial organization of activity persisted. Hence, a coarse spatial organization of functional activity maps is established very early during OB development when glomeruli are not yet differentiated. This spatial organization is maintained during development and growth of neuronal circuits and may have important functions for odor processing in larvae, for the differentiation of glomeruli, and for the refinement of activity maps at later developmental stages.

Animals↗

Differences in maternal supply and early development of closely related nematode species.

Comparative analyses revealed considerable differences in embryonic pattern formation and cell-specification between Caenorhabditis elegans and Acrobeloides nanus, members of two neighboring nematode clades. While C.elegans develops very rapidly, A. nanus needs 4-5 times as long. To investigate whether differences during early embryogenesis could be related to developmental tempo, we studied three more slowly developing representatives of the genus Rhabditis, thus close relatives of C.elegans. Besides differences in body size and mode of reproduction, they differ from C.elegans in the order of cleavages, germline behavior and requirement for early zygotic transcription, showing evident similarities to A. nanus. The distinct variations in cell-cycle rhythms and arrest after inhibition of transcription appear to reflect a species-specific interplay in the timing between exhausting maternal supplies and making available newly transcribed gene products. Looking for the reversal of cleavage polarity in the germline present in C.elegans but not in A. nanus, two of the studied species express this distinct feature only in a later cell generation. We found that a C.elegans mutant in the mes-1 gene shows a similar deviation. Concerning specification of the gut cell lineage and the potential to compensate for lost cells, the three tested Rhabditis species behave less regulatively, like C.elegans; in contrast to A. nanus, the gut precursor EMS requires an inductive signal from the germline cell P2 and an experimentally eliminated EMS cell is not replaced by a neighboring blastomere. In conclusion, embryogenesis of the examined Rhabditis species includes features of both the fast-developing C. elegans and the slow-developing A. nanus.

Animals↗

Dimerization of the largest subunit of chromatin assembly factor 1: importance in vitro and during Xenopus early development.

To date, the in vivo importance of chromatin assembly factors during development in vertebrates is unknown. Chromatin assembly factor 1 (CAF-1) represents the best biochemically characterized factor promoting chromatin assembly during DNA replication or repair in human cell-free systems. Here, we identify a Xenopus homologue of the largest subunit of CAF-1 (p150). Novel dimerization properties are found conserved in both Xenopus and human p150. A region of 36 amino acids required for p150 dimerization was identified. Deletion of this domain abolishes the ability of p150 to promote chromatin assembly in vitro. A dominant-negative interference based on these dimerization properties occurs both in vitro and in vivo. In the embryo, nuclear organization was severely affected and cell cycle progression was impaired during the rapid early cleaving stages of Xenopus development. We propose that the rapid proliferation at early developmental stages necessitates the unique properties of an assembly factor that can ensure a tight coupling between DNA replication or repair and chromatin assembly.

Amino Acid Sequence↗

Attractivity of male and female rats which are hormonally manipulated during early development and in adulthood.

Attractivity is one aspect of female sexuality relevant for the understanding of male-female sexual interactions. In a previous study, it was shown that intact males were equally attracted to early androgenized, gonadally intact females as to normally developed, estrous females. The present study was designed to investigate in what way hormones given in adulthood might influence attractivity of early androgenized females in adulthood. Specifically, we compared the attractivity of neonatally androgenized females (NeoTP) to the attractivity of normally developed females (NeoOIL), neonatally castrated males (NeoCASTR), and neonatally sham-castrated males (NeoSHAM) when different groups received either OIL, estradiol benzoate (EB) or testosterone propionate (TP) in adulthood. The male's preference to stay in the vicinity of one incentive in favor of the other was taken as an index of attractivity. The results show that, under the present hormonal conditions, NeoTP-females are generally less attractive than NeoOIL-females, more attractive than NeoSHAM-males, and equally attractive as NeoCASTR-males. TP-treated androgenized females were found to be equally attractive as TP-treated NeoSHAM-males. It is concluded that, relative to normally developed females, androgenized females become less attractive when the endogenous secretion of sex steroids is artifically controlled by gonadectomy and/or by administration of fixed amounts of sex steroids.

Animals↗

Early development of the primitive cranial vault in the chick embryo.

The calcified tissues involved in the early morphogenesis of the cranial vault were studied by microradiographic analysis and histological techniques in 12 chick embryos on the 9th, 12th, and 14th days of incubation. On the 9th day, the frontal, parietal, and squamosal bones are comprised of a thin lamina of chondroid tissue deposited at a short distance from the fibers of the dura mater. Woven bone formation takes place in the calvarial mesenchyme only after the 12th day of incubation and occurs mainly on the external side of the chondroid primordium. The present data obviously indicate that the primitive desmocranium of the chick embryo, which is usually known to be formed by intramembranous ossification, consists first of chondroid tissue. This tissue represents thus the initial modality of skeletogenic differentiation within the cephalic mesenchyme of the cranial vault.

Animals↗

Spatial and temporal distribution of Tie-1 and Tie-2 during very early development of the human placenta.

Vasculogenesis in the human placenta comprises differentiation and growth of newly forming blood vessels derived from hemangiogenic stem cells within the mesenchymal core of villi. In a second stage, angiogenesis leads to the expansion and remodeling of the already existing vessels. At present, relatively little is known about the regulatory mechanisms of vasculogenesis and angiogenesis during very early placentation. Using placental villous tissues from days 22 to 48 of pregnancy, we analyzed the spatial and temporal expression of Tie-1 and Tie-2 in parallel to vascular maturation in the human placenta. In immunohistochemistry both receptors, Tie-1 and Tie-2 show a cell and villous type specific expression during this early phase of placental development. Especially, cytotrophoblast and hemangiogenic cell cords in mesenchymal villi and Hofbauer cells in immature intermediate villi have the strongest immunoreactivities. Western blot analysis showed that no significant changes were detected for Tie-1 and Tie-2 as pregnancy advanced. Moreover, phospho-Tie-2 levels did not change significantly in parallel to pregnancy ages. We conclude that both receptors are involved in angiogenesis as well as vascular modulation of early vessels. Due to their spatial distribution we speculate on an additional role in regulation of villous and extravillous trophoblastic behavior.

Adult↗

Hepatic bile acid metabolism during early development revealed from the analysis of human fetal gallbladder bile.

A detailed study of the qualitative and quantitative composition of bile acids in human fetal gallbladder bile is described. Bile was collected during early gestation (weeks 16-19) and analyzed by gas chromatography and mass spectrometry, fast atom bombardment ionization mass spectrometry, and high performance liquid chromatography. Bile acids were separated into different conjugate groups by chromatography on the lipophilic anion exchange gel, diethylaminohydroxypropyl Sephadex LH-20. Quantitatively more than 80% of the bile acids were secreted into bile conjugated to taurine. Unconjugated bile acids and glycine conjugates accounted for 5-10% of the total biliary bile acids. Bile acid sulfates were present only in trace amounts indicating that quantitatively sulfation is not an important pathway in bile acid metabolism during development. Total biliary bile acid concentrations were low (0.1-0.4 mM) when compared to reported values for adult bile (greater than 10 mM). Chenodeoxycholic acid was the major biliary bile acid and exceeded cholic acid concentrations by 1.43-fold indicating either a relative immaturity in 12 alpha-hydroxylase activity during early life or a dominance of alternative pathways for chenodeoxycholic acid synthesis. A relatively large proportion of the biliary bile acids comprised metabolites not found in adult bile. The presence of relatively high proportions of hyocholic acid (often greater than cholic acid) and several 1 beta-hydroxycholanoic acid isomers indicates that C-1 and C-6 hydroxylation are important pathways in bile acid synthesis during development. We describe, for the first time, evidence for the existence of a C-4 hydroxylation pathway in the metabolism of bile acids, which may be unique to early human development. Mass spectrometry was used to confirm the identification of 3 alpha,4 beta,7 alpha-trihydroxy-5 beta-cholanoic and 3 alpha,4 beta-dihydroxy-5 beta-cholanoic acids. Quantitatively, these C-4 hydroxylated bile acids accounted for 5-15% of the total biliary bile acids of the fetus, suggesting that C-4 hydroxylation is quantitatively an important pathway in the bile acid metabolism during early life.

Bile↗

Norepinephrine- and isoproterenol- induced changes in cardiac contractility and cyclic adenosine 3':5' -monophosphate levels during early development of the embryonic chick.

Changes in contractility and cyclic adenosine 3':5'-monophosphate (cAMP) levels in response to norepinephrine and isoproterenol were monitored in isolated 4-day-old (noninnervated) and 7-day-old (innervated) embryonic hearts to determine whether a relationship between beta adrenergic receptor, adenylate cyclase and altered cardiac function is established at a very early stage in embryonic development before innervation takes place. Norepinephrine and isoproterenol promoted rapid time- and dose-dependent rises in cAMP levels which were greater in the 4-day-old hearts. These increases paralleled observed functional alterations within a specific range of drug concentrations and time. The elevation of cAMP levels and effect on cardiac function produced by isoproterenol (10(-7)M) were blocked by propranolol (10(-6)M). Dissociations between changes in tissue cAMP levels and cardiac function were also uncovered. Maximal increases in contractility were achieved with lower drug concentrations than were required to promote maximal accumulation of cAMP. Relatively high concentrations of norepinephrine or isoproterenol were less effective than lower concentrations in stimulating contractility but were more effective in promoting cAMP accumulation, The results indicate that both cardiac beta receptors adenylate cyclase are present and functionally related early in embryogenesis before sympathetic innervation occurs and that cAMP accumulation is associated with modulation of contractile activity whithin a certain concentration range and time course.

Adenylyl Cyclases↗

(Pro)insulin and insulin-like growth factor I complementary expression and roles in early development.

Evidence that the insulin-like growth factors play a role in embryonic as well as postnatal growth and central nervous system development has accumulated recently from studies using knock-out mice models. However, no effects of IGF-I and II have been demonstrated prior to organogenesis in these studies. We summarize here results supporting the role of insulin (or its precursor proinsulin) in vertebrate development prior to the expression of IGFs. (Pro)insulin mRNA is expressed in the chick embryo during neurulation and early organogenesis and its inhibition by antisense oligodeoxynucleotides increase apoptosis. In another system, proliferative neuroretina, (pro)insulin expression predominates over IGF-I expression. Modulation of apoptosis by (pro)insulin in retina may be largely responsible for the observed stimulation of DNA synthesis and neuronal differentiation. These effects are elicited as well by IGF-I, expressed later in neuroretina. Thus, these polypeptides have complementary expression in early embryos which suggests coordinated actions during development.

Animals↗

Early development of neuronal activity in the primate hippocampus in utero.

Morphological studies suggest that the primate hippocampus develops extensively before birth, but little is known about its functional development. Patch-clamp recordings of hippocampal neurons and reconstruction of biocytin-filled pyramidal cells were performed in slices of macaque cynomolgus fetuses delivered by cesarean section. We found that during the second half of gestation, axons and dendrites of pyramidal cells grow intensively by hundreds of micrometers per day to attain a high level of maturity near term. Synaptic currents appear around midgestation and are correlated with the level of morphological differentiation of pyramidal cells: the first synapses are GABAergic, and their emergence correlates with the growth of apical dendrite into stratum radiatum. A later occurrence of glutamatergic synaptic currents correlates with a further differentiation of the axodendritic tree and the appearance of spines. Relying on the number of dendritic spines, we estimated that hundreds of new glutamatergic synapses are established every day on a pyramidal neuron during the last third of gestation. Most of the synaptic activity is synchronized in spontaneous slow ( approximately 0.1 Hz) network oscillations reminiscent of the giant depolarizing potentials in neonatal rodents. Epileptiform discharges can be evoked by the GABA(A) receptor antagonist bicuculline by the last third of gestation, and postsynaptic GABA(B) receptors contribute to the termination of epileptiform discharges. Comparing the results obtained in primates and rodents, we conclude that the template of early hippocampal network development is conserved across the mammalian evolution but that it is shifted toward fetal life in primate.

Animals↗

Compensatory physiological responses to chronic blockade of amino acid receptors during early development in spontaneously active organotypic cerebral cortex explants cultured in vitro.

Paired organotypic explants from rat occipital cortex were cultured for up to three weeks in the presence of selective blockers of amino acid receptor blockers, during which period spontaneous action potential generation was monitored electrophysiologically. In contrast to isolated explants (Corner, M.A., van Pelt, J., Wolters, P.S., Baker, R.E.and Nuytinck, R.H. (2002) Physiological e.ects of sustained blockade of excitatory synaptic transmission on spontaneously active developing neuronal networks--an inquiry into the reciprocal linkage between intrinsic biorhythms and neuroplasticity in early ontogeny. Neurosci. Biobehav. Rev., 26: 127-185), which upregulated their initially depressed spontaneous bursting activity only under conditions of N-methyl D-aspartate (NMDA) receptor blockade, cross-innervated co-cultures showed a large degree of functional recovery even when combined NMDA and AMPA receptor blockade was carried out. This compensatory activity could be eliminated by acute addition of a selective kainate receptor blocker to the medium. When kainate along with AMPA and NMDA receptor mediated activity was chronically suppressed, however, considerable functional recovery--in the form of recurrent burst discharges--took place gradually over a period of three weeks in vitro. These spontaneous bursts disappeared rapidly upon treatment with the muscarinic receptor blocker, atropine, but continuous low-level firing emerged at the same time. Similar "tonic" background activity was induced in control cultures as well, but without any noticeable reduction in burst discharges. Co-cultured neocortex explants, in which cyto-morphological maturation proceeds to a far greater degree than in isolated explants (Baker, R.E.and van Pelt, J. (1997) Co-cultured but not isolated cortical explants display normal dendritic development: a longterm quantitative study. Dev. Brain Res., 98: 21-27) are evidently capable of an astonishing degree of functional compensation for loss of excitatory synaptic drive during development. It could be shown, furthermore, that such homeostatic responses are not mediated largely by a weakening of inhibitory mechanisms in the absence of spontaneous firing. Chronic inhibitory synaptic blockade, on the other hand, led to intensified bursting activity which gradually normalized over a 3-week culture period. The cellular basis for this reversal of the disinhibited state, as well as for the residual neuronal firing even after cholinergic mechanisms have been largely eliminated, is at present unknown. The degree to which immature cortical networks attempt to compensate for altered levels of physiological activity, as documented in the present report, is another indication of how important such activity can be for normal development (see Corner, M.A., van Pelt, J., Wolters, P.S., Baker, R.E. and Nuytinck, R.H. (2002) Physiological e.ects of sustained blockade of excitatory synaptic transmission on spontaneously active developing neuronal networks-an inquiry into the reciprocal linkage between intrinsic biorhythms and neuroplasticity in early ontogeny. Neurosci. Biobehav. Rev., 26: 127-185).. At the same time, the large variations in overall firing levels and "macro-scale" temporal patterns from culture to culture within a given series, despite all attempts at identical preparation of the explants, can only mean that the "set-points" for such regulation are themselves subject to unknown ontogenetic factors which, apparently, are nonuniformly distributed even within a restricted region of the neocortex. On the other hand, it was striking to note that, regardless of age or treatment, an unexpected degree of consistency in temporal patterning existed at "mini-" and "micro-" time-scales (viz., EEG delta and beta frequency ranges, respectively) even when network bursting tendencies became greatly reduced in favor of tonic firing.

Adaptation, Physiological↗

Expression of activin mRNA during early development in Xenopus laevis.

Activins are members of the transforming growth factor-beta superfamily, a class of peptide growth factors that can regulate the growth and differentiation of a variety of cell types. In mesoderm induction assays, activins A and B were shown to be very potent inducers and it was only recently demonstrated that they are crucial for initial mesoderm induction in Xenopus embryos. To determine the source of activin protein for initial mesoderm induction and to investigate whether activins may play further roles in embryonic development we have examined the localization of the mRNAs encoding the activin beta A and beta B subunits in Xenopus embryos. Activin beta A and beta B mRNAs are found in the follicle cells surrounding oocytes but not in oocytes themselves or fertilized eggs. During embryogenesis activin mRNA is first detected after the midblastula transition and expression increases as development proceeds. Activin beta B mRNA is homogeneously distributed during blastula and early gastrula stages but restricted to the dorso-anterior region in neurula stage embryos. At the early tailbud stage activin expression becomes confined to the brain, eye analgen, visceral pouches, otic vesicles, and the anterior notochord.

Activins↗