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Cotransplantation of embryonic mouse retina with tectum, diencephalon, or cortex to neonatal rat cortex.

Retinae from embryonic mice were transplanted to the occipital cortex of neonatal rats together with their normal target regions, tectum or diencephalon, from embryonic mice or rats. In control experiments, retinae were cotransplanted with embryonic rat occipital cortex. In over 80% of the experimental animals, both transplants differentiated and grew. Ganglion cells in the retinae cotransplanted close to tectum or diencephalon survived for at least 15 weeks. Their survival was associated with the development of a distinct optic fiber layer and outgrowth of axons from the transplanted mouse retina. Specific innervation of distinct patches within the cotransplanted rat tectum or diencephalon was demonstrated by the use of an anti-mouse antibody. The innervated regions, which could be as far away as 1.3 mm from the retinae, were correlated with cytological features of the cotransplanted tectum or diencephalon. By contrast, the host cortex was never innervated by the transplanted retinae. In the control animals in which the retinae were cotransplanted with occipital cortex and in four animals in which the cotransplants lay more than 2.7 mm apart, no ganglion cells were identified and there was no evidence of an optic fiber layer, outgrowth of axons, or innervation. These results support the idea that in order to survive, retinal ganglion cells need to innervate an appropriate target region. Further, the specific innervation of regions within the cotransplanted tectum or diencephalon suggests that these target regions are able to exert a tropic influence on the axons of retinal ganglion cells, even in the absence of many of the normal structure cues.

Animals↗

Tissue interactions in the induction of anterior pituitary: role of the ventral diencephalon, mesenchyme, and notochord.

Rathke's pouch, the epithelial primordium of the anterior pituitary, differentiates in close topographical and functional association with the ventral diencephalon. It is still not known whether the ventral diencephalon acts as the initial inducer of pituitary development. The roles of the adjacent mesenchyme and notochord, two other tissues located in close proximity to Rathke's pouch, in this process are even less clear. In this report we describe an in vitro experimental system that reproduces the earliest steps of anterior pituitary development. We provide evidence that the ventral diencephalon from 2- to 4-day-old chick embryos is able to function as an inducer of pituitary development and can convert early chick embryonic head ectoderm, which is not involved normally in pituitary development, into typical anterior pituitary tissue. This induction is contact-dependent. In our experimental system, there is a requirement for the supporting action of mesenchyme, which is independent of the mesenchyme source. Transplantation of the notochord into the lateral head region of a six-somite chick embryo induces an epithelial invagination, suggesting that the notochord induces the outpouching of the roof of the stomodeal ectoderm that results in formation of Rathke's pouch and causes the close contact between this ectoderm and the ventral diencephalon. Finally, we demonstrate that the ventral diencephalon from e9.5-e11.5 mouse embryos is also an efficient inducer of anterior pituitary differentiation in chick embryonic lateral head ectoderm, suggesting that the mechanism of anterior pituitary induction is conserved between mammals and birds, using the same, or similar, signaling pathways.

Animals↗

Effects of selective serotonin and serotonin/noradrenaline reuptake inhibitors on extracellular serotonin in rat diencephalon and frontal cortex.

Some clinical reports suggest that tricyclic antidepressants which block both noradrenaline and serotonin (5-HT) reuptake (SNRIs) are more effective than selective 5-HT reuptake inhibitors (SSRIs) in treating severe depression. Moreover, one neurochemical study reported larger increases in extracellular 5-HT in rat frontal cortex in response to the tricyclic antidepressant imipramine compared to the SSRI fluoxetine. However, imipramine, which blocks both 5-HT and noradrenaline reuptake, also binds with relatively high affinity to receptors for noradrenaline, histamine and acetylcholine. Thus, to test the hypothesis that compounds that inhibit both 5-HT and noradrenaline reuptake produce larger increases in 5-HT efflux, we compared the effects of acute systemic administration of several SNRIs and SSRIs. Extracellular 5-HT was measured using microdialysis probes implanted in the diencephalon and frontal cortex of unanesthetized rats. We tested the SSRIs paroxetine (0.3-10 mg/kg), citalopram (10-20 mg/kg) and fluoxetine (10 mg/kg), the nonselective tricyclic antidepressant imipramine (20 mg/kg) and the more selective SNRIs duloxetine (3-30 mg/kg) and venlafaxine (30-50 mg/kg). During the lights-off period, paroxetine and duloxetine increased 5-HT in the diencephalon approximately 300 and approximately 200%, respectively. During the lights-on period, paroxetine and duloxetine each increased 5-HT approximately 400% in the diencephalon. In the frontal cortex, both paroxetine and duloxetine increased 5-HT approximately 200%. Citalopram and venlafaxine each increased 5-HT in the diencephalon approximately 300%. Fluoxetine and imipramine increased 5-HT in the diencephalon by approximately 125 and approximately 80%, respectively. Thus, these results do not support the hypothesis that compared to SSRIs, compounds which inhibit both 5-HT and noradrenaline reuptake have a larger acute effect on extracellular 5-HT.

Adrenergic Uptake Inhibitors↗

Choice of either beta-catenin or Groucho/TLE as a co-factor for Xtcf-3 determines dorsal-ventral cell fate of diencephalon during Xenopus development.

Co-repressor Groucho/Transducin-Like Enhancer of split (TLE) interacts with transcription factors that are expressed in the central nervous system (CNS), and regulates transcriptional activities. In this study, we examined the contribution of Groucho/TLE to CNS development in Xenopus. The functional inhibition of Groucho/TLE using the WRPW motif as a competitor resulted in the conversion of the ventral cell into the dorsal fate in the prospective diencephalon. We also found that the neural plate was expanded laterally without inhibiting neural crest development. In tailbud, the disturbance of trigeminal ganglion development was observed. These observations allow us to conclude that Groucho/TLE plays important roles in the induction and patterning of distinct CNS territories. We found that Xtcf-3 is involved in some of the patterning in these territories. We generated the variant of Xtcf-3, Xtcf-3BDN-, which is suspected to interfere with the interaction between endogenous Groucho/TLE and Xtcf-3. The transcriptional activation of the Xtcf-3-target genes in response to endogenous Wnt/beta-catenin signaling by the overexpression of Xtcf-3BDN- led to a reduction of the ventral diencephalon. This result indicates that transcriptional repression by the Groucho/TLE-Xtcf-3 complex is important for ventral diencephalon patterning. This idea is supported by the finding that the overexpression of the dominant-negative form of Xtcf-3 or axil causes the expansion of the ventral diencephalon. Based on these data, we propose that the localized activation of Wnt/beta-catenin signaling, which converts Tcf from a repressor to an activator, is required for the establishment of dorsal-ventral patterning in the prospective diencephalon.

Amino Acid Motifs↗

The rostral and caudal boundaries of the diencephalon.

Knowledge of nature and features of the boundaries between the main neural regions seems to be essential to understand the rules of brain regionalization. On the light of several current and classical criteria used to define cerebral boundaries, we examine the features of the places recognized as rostral and caudal boundaries in the developing diencephalon and provide new images about the glial features of these boundaries. One demonstrated property of some embryonic boundaries is the prevention of the crossing cells in the early ventricular zone (clonal restriction), while the intermediate zone seems to lack it. Data available so far indicate that the early boundary between diencephalon and mesencephalon (d/m) is a clonal restriction limit, but not between diencephalon and telencephalon (d/t). Later, while diencephalic nuclei form, cellular dispersion does not occur through the alar part of d/m, but it achieves in the corresponding d/t alar portion. The relationship between origin, migration, and cell-type specification of neural cells is being the object of special attention in the telencephalon, where specific cellular fenotipes can migrate to distant regions following non-radial routes. Such is the case of most GABAergic interneurons of avian and mammalian pallium and oligodendrocytes of the forebrain. In this regard, little attention has been devoted to the diencephalon, where this type of migration, specially those through the rostral boundary, has been reported by different authors. We introduce increasing evidence about non-conventional neuronal migration in the developing diencephalon and compare the reported migratory behavior with respect to both boundaries.

Animals↗

Fate map of the diencephalon and the zona limitans at the 10-somites stage in chick embryos.

The diencephalon is a central area of the vertebrate developing brain, where the thalamic nuclear complex, the pretectum and the anterior tegmental structures are generated. It has been subdivided into prosomeres, which are transversal domains defined by morphological and molecular criteria. The zona limitans intrathalamica is a central boundary in the diencephalon that separates the posterior diencephalon (prosomeres 1 and 2), from the anterior diencephalon (prosomere 3). This intrathalamic limit appears early on in neural tube development, and the molecular pattern that it reveals suggests an important role in the diencephalic histogenesis. We hereby present a fate map of the presumptive territories in the diencephalon of a chick embryo at the 10-11 somite stages (HH9-10), by homotopic and isochronic quail-chick grafts. The anatomical interpretation of chimeric brains was aided by correlative whole-mount in situ hybridization with RNA probes for chicken genes expressed in specific diencephalic territories. The resulting fate map describes the distribution of the presumptive diencephalic prosomeres in the neural tube, and demonstrates their topologically conserved relationships throughout the neural development. Moreover, we show that the presumptive epithelium of ZLI can be localized at early developmental stages in the diencephalic alar plate at the anterior limit of the Wnt8b gene expression domain.

Animals↗

Distribution of galanin immunoreactivity in the sheep diencephalon.

Although the physiological role of galanin has been demonstrated in several endocrine regulations in sheep, the anatomical characteristics of this neuronal system has never been studied. The distribution of galanin-containing neurones was described by immunohistochemistry using galanin antiserum in the diencephalon of adult ewes, both ovariectomized or treated with colchicine. Galanin-immunoreactivity was found throughout the diencephalon. In the ovariectomized ewes, galanin-immunoreactive neurones were mainly observed in the medial preoptic area and the infundibular nucleus. The highest density of immunoreactive fibres was found in the external layer of the median eminence. Numerous galanin-immunoreactive fibres were also observed in the preoptic area, the mediobasal hypothalamus, the periphery of the supraoptic and the paraventricular nuclei. With colchicine treatment, the number of labelled neurones increased, and additional galanin-immunoreactive perikarya were observed in the bed nucleus of the stria terminalis, the lateral septum, the supraoptic, the paraventricular and the periventricular nuclei and the paraventricular nucleus of the thalamus. In the caudal part of the diencephalon, the density of labelled neurones was lower in both groups of animals than in other species studied. Regardless of treatment, labelling was not seen in the suprachiasmatic nucleus and only rarely in the ventromedial nucleus. These results describe, for the first time, the distribution of galanin-immunoreactive neurones in the sheep diencephalon. Compared to other species studied, distribution in the sheep diencephalon has several distinct differences. In ovariectomized animals, the medial preoptic area presents more labelled neurones in sheep than in monkeys, whereas in the supraoptic nucleus the density of labelled neurones is lower in sheep than in humans or opossums. After colchicine treatment only very few differences were observed between sheep and rats, but in contrast to other species, the suprachiasmatic nucleus of the sheep does not contain labelled neurones.

Animals↗

The diencephalon of the channel catfish, Ictalurus punctatus. II. Retinal, tectal, cerebellar and telencephalic connections.

In a companion paper, the nuclear organization of the diencephalon of the channel catfish, Ictalurus punctatus, was described and compared to that of other teleosts. The present paper describes the connections of the diencephalon with the retina, optic tectum, corpus of the cerebellum and telencephalon. The principal tracer employed is the indocarbocyanine dye DiI which diffuses along neuronal membranes in fixed tissues. Almost all of the nuclei that were recognized as distinct in the companion study are found to also exhibit distinct sets of connections. Most of these connections have not been described previously in catfishes or other teleosts. When combined with connectional data from the existing literature, the results of the present study allow one to recognize a great number of distinct pathways through the diencephalon of channel catfish, including several visual, auditory, gustatory, electrosensory and mechanosensory pathways to the telencephalon. Almost all of the species differences in diencephalic organization noted in the companion study can be accounted for by changes in one of the major sensory pathways. In contrast, the multimodal and integrative areas of the diencephalon appear to be relatively conservative. A comparison between the diencephalon of teleosts and that of other vertebrates suggests that the dorsal thalamus, the ventral thalamus and the posterior tuberculum are homologous, at least in part, to the dorsal thalamus, the zona incerta and the subthalamic nucleus of mammals, respectively. All three areas project to the telencephalon in both mammals and teleosts. In most vertebrates, however, the dorsal thalamus provides the dominant input to the telencephalon, whereas in teleosts the main telencephalic input derives instead from the posterior tuberculum.

Animals↗

A study of overlap and collateralization of bulbar reticular and raphe neurons which project to the spinal cord and diencephalon of the North American opossum.

Labeled neurons were found in most reticular and raphe nuclei of the opossum's medulla after horseradish peroxidase (HRP) injections into either the spinal cord or diencephalon. The labeling produced by spinal injections differed somewhat from that produced by diencephalic ones, but HRP-positive neurons were found in what appeared to be comparable areas. In order to study the intermingling of bulbospinal and bulbodiencephalic neurons more directly, we used fluorescent markers (true blue, nuclear yellow and diamidino yellow dihydrochloride) in double-labeling experiments. When injections of one dye into the spinal cord were combined with injections of another into the diencephalon, neurons labeled by one or the other marker were found to be intermingled in most reticular and raphe nuclei. The double-labeling experiments also showed that some neurons of the bulbar reticular formation and raphe project to both the spinal cord and diencephalon, presumably by axonal collaterals. The number of such neurons represents a somewhat larger proportion of those projecting to the diencephalon than to the spinal cord. It appears, however, that most neurons project either to the spinal cord or to the diencephalon and do not provide collaterals to both areas.

Animals↗

Patterning the zebrafish diencephalon by the conserved zinc-finger protein Fezl.

The forebrain constitutes the most anterior part of the central nervous system, and is functionally crucial and structurally conserved in all vertebrates. It includes the dorsally positioned telencephalon and eyes, the ventrally positioned hypothalamus, and the more caudally located diencephalon [from rostral to caudal: the prethalamus, the zona limitans intrathalamica (ZLI), the thalamus and the pretectum]. Although antagonizing Wnt proteins are known to establish the identity of the telencephalon and eyes, it is unclear how various subdivisions are established within the diencephalon--a complex integration center and relay station of the vertebrate brain. The conserved forebrain-specific zinc-finger-containing protein Fezl plays a crucial role in regulating neuronal differentiation in the vertebrate forebrain. Here, we report a new and essential role of zebrafish Fezl in establishing regional subdivisions within the diencephalon. First, reduced activity of fezl results in a deficit of the prethalamus and a corresponding expansion of the ZLI. Second, Gal4-UAS-mediated fezl overexpression in late gastrula is capable of expanding the prethalamus telencephalon and hypothalamus at the expense of the ZLI and other fore- and/or mid-brain regions. Such altered brain regionalization is preceded by the early downregulation of wnt expression in the prospective diencephalon. Finally, fezl overexpression is able to restore the anterior forebrain and downregulate wnt expression in Headless- and/or Tcf3 (also known as Tcf7l1a)-deficient embryos. Our findings reveal that Fezl is crucial for establishing regional subdivisions within the diencephalon and may also play a role in the development of the telencephalon and hypothalamus.

Animals↗

Induced expression of c-fos in the diencephalon and pituitary gland of goats following transportation.

To identify regions of the caprine diencephalone and pituitary gland related to transportation stress, the expression of c-fos protein was examined immunohistochemically as an indicator of neural activation. Ten castrated Shiba goats (Capra hircus), five transported and five controls, were used. Transported goats were trucked for 1 h and killed by transcardiac perfusion 1 h after the end of transportation. Control goats were housed in single pens killed in the same manner and at the same time as the transported goats. The diencephalon and the pituitary gland were removed after perfusion and used for immunostaining. Plasma cortisol concentrations during and after transportation also were investigated. During transportation, plasma cortisol concentrations increased (P < 0.05) compared with those in the controls. In the diencephalon, c-fos immunoreactive cells were detected in the subcallosa, the lateral septal area, the bed nucleus of stria terminalis (BNST), the preoptic hypothalamic area (POA), the suprachiasmatic nucleus (SCN), the supraoptic nucleus, the paraventricular hypothalamic nucleus parvocellular (PVNp), the paraventricular hypothalamic nucleus magnocellular (PVNm), the arcuate nucleus (ARC), the paraventricular thalamic nucleus, and the stria medullaris in both control and transported goats. The numbers of c-fos immunoreactive cells were increased (P < 0.05) by transportation in the PVNm, the PVNp, the BNST, the POA, the ARC, and the SCN (P < 0.10). In the anterior pituitary gland, the number of c-fos immunoreactive cells in transported goats was 4 to 30 times as much as in control goats; however, there were no differences in the intermediate and posterior lobes between control and transported goats. This study has identified regions in the caprine diencephalon and pituitary gland that show transport-induced increases in c-fos immunoreactive cells. In conclusion, the PVNm, the PVNp, the BNST, the POA, the SCN in the diencephalons, and the anterior lobe of pituitary gland may be involved in the stress responses of goats to transportation.

Animal Husbandry↗

Distribution of muscimol, QNB, and 5HT binding in the vertebrate diencephalon: a comparative study of eight mammals and three non-mammals.

The distribution of muscimol, quinuclidinyl benzilate (QNB), and serotonin (5HT)-bound receptors in the diencephalon was examined by conventional receptor-binding methods in 11 species of amniotes including 2 reptiles, 1 bird, and 8 mammals, selected mostly on the basis of their differing last common ancestor with Anthropoids. We found that receptor binding can help define major subdivisions of the forebrain. The results show that in each of these species, the distribution of muscimol and QNB binding across the four major subdivisions of the diencephalon was consistent; densest in the dorsal thalamus, with hypothalamus and then either ventral thalamus or epithalamus with successively lesser amounts. However, the binding of serotonin (5HT) was most prevalent in the hypothalamus with equivalent amounts in the other diencephalic subdivisions. Myelin- and cell-stained materials showed that the pattern of high-density binding probably is not the secondary result of non-neurochemical factors such as differences in cell or neuropil density or in total available membrane. Perhaps more importantly, the receptor distributions suggest functional roles for major subdivisions across taxa. Results show that GABA-A and muscaranic Ach receptors are common in the dorsal diencephalon across vertebrate species and, therefore, are probably responsible for the gating of information to the cortex. Results show that serotonin is predominant in the hypothalamus. The lack of it in the dorsal thalamus indicates that it is probably not responsible for gating of information to the cortex. Results also show that in nonmammals the amount of GABA-A and muscaranic Ach differs from that found in mammals. For muscaranic Ach, the labeling in marsupials differs from that in placentals. Primates differ from other species (nonmammals and mammals combined) in the amount of 5HT found in the ventral diencephalon and the hypothalamus.

Animals↗

Axonal growth from the habenular nucleus along the neuromere boundary region of the diencephalon is regulated by semaphorin 3F and netrin-1.

In neural development, major tracts are often formed along the neuromere boundary regions, although the molecular mechanism underlying this formation remains to be clarified. In the diencephalon, axons from the habenular nucleus extend along the neuromere boundary region between p1 and p2. At embryonic days 13-15, among members of class 3 semaphorins, only semaphorin 3F (Sema3F) was expressed in the diencephalon. Sema3F, which was strongly expressed in the rostral p1, repulsed axons from habenular explants. While p2 explants did not exert a repulsive effect on axons from habenular explants at a distance, habenular axons did not grow into p2 explant. Explants from the ventral region of the caudal diencephalon where netrin-1 is expressed attracted the axons from habenular explants. The attractive effect was blocked by an antibody for DCC. These results suggest that the growth of axons from the habenular nucleus along the neuromere boundary region may be regulated by Sema3F from the rostral p1, and netrin-1 from the ventral region of the caudal diencephalon.

Animals↗

The origin of projections from the medullary reticular formation to the spinal cord, the diencephalon and the cerebellum at different stages of development in the North American opossum: studies using single and double labeling techniques.

We have employed the retrograde transport of horseradish peroxidase alone or conjugated to wheat germ agglutinin, to label neurons within the medullary reticular formation which project to the spinal cord, the diencephalon and the cerebellum at different stages of development in the North American opossum. At selected ages, the fluorescent markers Fast Blue and Diamidino Yellow were also used in double-labeling experiments to determine if single neurons innervate both the spinal cord and diencephalon or the spinal cord and cerebellum, presumably via axonal collaterals. The opossum was employed because it is born in a very immature state, 12 days after conception, and is thus available for injections at early stages of development. At all ages studied, the location of retrograde labeling within the medullary reticular formation after spinal, diencephalic or cerebellar placements of horseradish peroxidase or its conjugate appeared similar to that obtained in the adult animal. Such results suggest that the origin of projections from the medullary reticular formation to the areas injected is specified early in development. At some ages, however, the labeling density appeared greater than in the adult animal. When either Fast Blue or Diamidino Yellow was injected into the spinal cord and the other marker was placed into the diencephalon at such ages, relatively few neurons of the medullary reticular formation were double-labeled. When one marker was injected into the spinal cord and the other was placed within the cerebellum, no double-labeled neurons were found. These results indicate that at the ages studied, relatively few neurons of the medullary reticular formation provide collateral innervation to either the spinal cord and diencephalon or the spinal cord and cerebellum. Similar conclusions have been reached previously for the adult opossum. We have interpreted our results to suggest that the organization of reticular projections, at least to the areas injected, may not be shaped by the selective elimination of axonal collaterals as in certain other areas of the brain.

Amidines↗

Disruption of PAX6 function in mice homozygous for the Pax6Sey-1Neu mutation produces abnormalities in the early development and regionalization of the diencephalon.

Pax6 expression in the diencephalon of the mouse embryo is restricted both antero-posteriorly and dorso-ventrally, with changes in level occurring at prosomere boundaries. Small eye (Pax6Sey-1Neu) mice homozygous for Pax6 mutations have multiple defects in early forebrain development. In the diencephalon of Pax6Sey-1Neu/Pax6Sey-1Neu mice there is an apparent enlargement of the zona limitans (the boundary region between prosomeres p2 and p3), and a blurring of the p1-p2 boundary. PAX6 function is also required for the normal development of the posterior commissure at the midbrain-p1 boundary. In the posterior diencephalon PAX6 appears to regulate its own transcription, and that of Wnt7b. In p2 and p3, ventral markers are expressed more dorsally than normal, and this is accompanied in p3 by a reduction in the size of the zona incerta. Thus, PAX6 is essential for the normal development and regionalization of the diencephalon.

Animals↗

Seasonal variation in androgen-metabolizing enzymes in the diencephalon and telencephalon of the male European starling (Sturnus vulgaris).

In seasonally breeding songbirds, seasonal fluctuations occur in serum testosterone (T) concentrations and reproductive behaviours. Many T-dependent behaviours are regulated by the activity of androgenic and oestrogenic metabolites within specific brain regions. Male European starlings breed in spring when circulating T concentrations peak. T and its metabolites act within portions of the diencephalon to regulate the pituitary-gonadal axis and to activate courtship and copulation. Song in male starlings is critical for mate attraction during the breeding season and is regulated by steroid-sensitive nuclei in the telencephalon and diencephalon. Outside the breeding season, T is undetectable, however, males continue to sing at high levels. This suggests that singing outside of the breeding season might not be T-dependent as it appears to be in the spring. Alternatively, singing when T is low might continue to be regulated by T due to increased sensitivity of the brain to the action of the steroid. This increased sensitivity could be mediated by changes in intracellular T metabolism leading to increased production of active or decreased production of inactive metabolites. To explore the relationship between T-metabolism and reproductive behaviour, we analysed seasonal changes in the activity of four brain T-metabolizing enzymes: aromatase, 17beta-hydroxysteroid dehydrogenase (17beta-HSDH), 5alpha-reductase (all three convert T into active metabolites) and 5beta-reductase (converts T into an inactive metabolite) in the diencephalon and telencephalon. In the anterior and posterior diencephalon, the highest aromatase was observed in spring when this region is critical for courtship and copulation. In the telencephalon, aromatase was highest and 5beta-reductase was lowest throughout the winter months well prior to the reproductive season and these enzymes presumably maximize T-activity within this region. Although these data do not indicate whether the metabolic changes occur specifically within song nuclei, these findings are compatible with the idea that singing in male starlings outside the breeding season may be regulated by steroids despite the presence of low serum T concentrations. Overall, seasonal changes in T-metabolizing enzymes appear to play a significant role in seasonal changes in behaviour and reproductive physiology.

17-Hydroxysteroid Dehydrogenases↗

Coordinated expression of Hoxa2, Hoxd1 and Pax6 in the developing diencephalon.

Coordinated expression of Hoxa2, Hoxd1 and Pax6 proteins were found to coincide with the three developmental stages of the diencephalon, as described for the mouse brain. In the first stage (embryonic day (E) 10-12) Hoxa2, Hoxd1 and Pax6 (an early marker gene of the diencephalon) were expressed as early as E10.5 in prosomeres (p), p2 and p3. All three proteins continue to exhibit overlapping domains of expression at E12.5-13 (beginning of the second stage) when the primitive dense cell layer begins to differentiate into the internal germinal, external germinal and mantle layers. Towards the end of the second stage (E15), Pax6 expression was down-regulated whereas Hoxa2 and Hoxd1 continued to exhibit overlapping domains of expression for both protein and mRNA. Hoxd1 expression decreased significantly in the third stage of diencephalic development (E16-postnatal) such that only Hoxa2 expression persisted in the diencephalon of newborn mice. The temporal and spatial expression of these three proteins imply that coordinated waves of Hoxa2, Hoxd1 and Pax6 expression may be required to provide positional information for the specification of the diencephalon.

Animals↗

Evidence of haematopoiesis within the developing human diencephalon. Correlations with vertebrate phylogeny.

AIM: The sites of haematopoiesis during human ontogeny can be correlated to the sites where haematopoiesis occurs in vertebrate phylogeny. As haematopoiesis has been described in the diencephalon and pituitary gland of water-inhabiting vertebrates we wanted to find out whether such a phenomenon also occurs in human embryos. MATERIAL AND METHODS: Paraffin-embedded specimens from the diencephalon and pituitary gland of human embryos at the 7th to 22nd gestational week and from adults were investigated by conventional histology and immunohistology for the presence of haematopoietic cells. RESULTS: Cellular accumulations predominantly of erythroid and megakaryocytic lineage were identified in the floor of the developing diencephalon of the 7th/8th gestational week. At the older developmental stages of the 18th to 22nd gestational week loose aggregates of haematopoietic cells within the leptomeningeal spaces adjacent to the hypophyseal infundibulum were detected in 2 out of 7 cases analyzed. CONCLUSIONS: As it has been proposed that lymphohaematopoietic clusters occasionally occur within the brain in bone marrow-less vertebrates as a response to noxious agents, we speculate that this temporal appearance of haematopoietic cell clusters within the diencephalon floor in early human ontogeny could also be due to fetal immunomodulations.

Animals↗