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J I Morgan

Publications and source records attributed to J I Morgan.

At least 73 records · Page 4Linked to original sources
PubMed1993

Regulation of proto-oncogene expression in adult and developing lungs.

Activation of immediate-early gene expression has been associated with mitogenesis, differentiation, nerve cell depolarization, and recently, terminal differentiation processes and programmed cell death. Previous evidence also suggested that immediate-early genes play a role in the physiology of the lungs (J. I. Morgan, D. R. Cohen, J. L. Hempstead, and T. Curran, Science 237:192-197, 1987). Therefore, we analyzed c-fos expression in adult and developing lung tissues. Seizures elicited by chemoconvulsants induced expression of mRNA for c-fos, c-jun, and junB and Fos-like immunoreactivity in lung tissue. The use of pharmacological antagonists and adrenalectomy indicated that this increased expression was neurogenic. Interestingly, by using a fos-lacZ transgenic mouse, it was shown that Fos-LacZ expression in response to seizure occurred preferentially in clusters of epithelial cells at the poles of the bronchioles. This was the same location of Fos-LacZ expression detected during early lung development. These data imply that pharmacological induction of immediate-early gene expression in adult mice recapitulates an embryological program of gene expression.

Adrenalectomy↗
PubMed1993

A fos-lac Z transgenic mouse that can be used for neuroanatomic mapping.

Cellular immediate-early genes are rapidly induced by a diverse range of agents and conditions. Since many cIE genes encode known or potential transcription factors, they are believed to couple extracellular stimuli to long-lasting alterations in cellular phenotype through the regulation of gene transcription. In addition, the localization of the products of cIE genes has been used as a method for determining the cellular sites of action of particular agents in the nervous system. However, the methods of analysis are tedious, and the results may be ambiguous because of cross-reaction of reagents with related proteins. To further the utility of this approach, a bacterial gene encoding beta-galactosidase (lac Z) has been fused, in frame, into the fourth exon of c-fos, and this fos-lac Z fusion gene has been introduced into the germ line of mice. We have analyzed the expression of beta-galactosidase (under the control of the c-fos promoter) in the developing and adult nervous systems of these transgenic mice. As far as can be determined, the constitutive and stimulated expression of the transgene accurately reflects the expression of cognate c-fos in both cultured cells and the intact animal. This study has also revealed novel sites of constitutive and induced expression of c-fos that were overlooked using conventional analysis. In particular, constitutive expression of c-fos is associated with cells that are entering terminal differentiation and are destined to die. In addition, induced expression of the transgene in adult brain mirrors the pattern of neurotoxicity elicited by kainic acid.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Temporal and spatial expression of a fos-lacZ transgene in the developing nervous system.

A Fos-lacZ transgenic mouse has been described that accurately recapitulates both constitutive and inducible patterns of c-fos expression in adult mice. Here we describe the developmental expression of the transgene in the brain during the early postnatal period. On the day of birth, expression of the transgene is observed in several discrete regions of the CNS; including the olfactory bulb, hippocampus, retrosplenial cortex, parafascicular nucleus of the thalamus, and several cranial nerve nuclei. In these regions, expression declines to adult levels by three weeks. In other regions of the CNS, expression appeared transiently after P0.

Animals↗
PubMed1992

fos-lacZ transgenic mice: mapping sites of gene induction in the central nervous system.

A transgenic mouse line containing a fos-lacZ fusion gene was derived in which beta-galactosidase activity identified cell populations expressing fos either constitutively or after stimulation. Seizures and light pulses induced nuclear lacZ activity in defined populations of neurons in vivo, and an array of neurotransmitters, including glutamate, induced the transgene in primary brain cultures. In unstimulated mice, the major sites of fos-lacZ expression were skin, hair follicle, and bone. fos-lacZ mice provide a new avenue for activity mapping studies based on gene expression.

Adrenal Glands↗
PubMed1992

The future of hypnosis through the remainder of the decade: a Delphi poll.

We predicted the future of hypnosis for the next 10 years using the Delphi method--the best available forecasting tool. A panel of 89 experts in the field of hypnosis completed a 44-item questionnaire that addressed future developments in these areas: (1) training and preparation, (2) general applications of hypnosis, (3) theory, and (4) research. Also predicted was the likelihood of occurrence of certain cogent events in the field. Results indicated probable increases in emphasis in nearly all areas surveyed. We also solicited nominations for major contributors to the field of hypnosis, major books on hypnosis, and journals most likely to publish articles on hypnosis.

Adult↗
PubMed1991

Dynamic organization of developing Purkinje cells revealed by transgene expression.

The cerebellum has many properties that make it a useful model for investigating neural development. Purkinje cells, the major output neurons of the cerebellar cortex, have drawn special attention because of the availability of biochemical markers and mutants that affect their development. The spatial expression of L7, a protein specific for Purkinje cells, and L7 beta Gal, a gene expressed in transgenic mice that was constructed from the L7 promoter and the marker beta-galactosidase, delineated bands of Purkinje cells that increased in number during early postnatal development. Expression of the transgene in adult reeler mutant mice, which show inverted cortical lamination, and in primary culture showed that the initial expression of L7 is intrinsic to Purkinje cells and does not depend on extracellular signals. This may reflect an underlying developmental map in cerebellum.

Aging↗
PubMed1991

Regulation of a fos-lacZ fusion gene: a paradigm for quantitative analysis of stimulus-transcription coupling.

Expression of the c-fos protooncogene is induced by a great variety of extracellular stimuli. A fos-lacZ fusion gene has been constructed that recapitulates this regulation. The fos-lacZ gene was introduced into B104 neuroblastoma cells for use in a quantitative assay for stimulus-transcription coupling. Both alpha- and beta-adrenergic agonists, dibutyryl cAMP, and phorbol ester induced beta-galactosidase activity in a dose-dependent manner. Thus, the interactions of receptors with agonists and antagonists, as well as intracellular second messenger-mediated signaling events, can be analyzed quantitatively. This approach represents a prototypic method for investigating stimulus-response coupling based upon gene expression.

Animals↗
PubMed1991

Cerebellar Purkinje cell markers are expressed in retinal bipolar neurons.

Previous studies have been directed at the elucidation of neuron-specific gene expression in the mammalian central nervous system. In particular, we have identified a series of marker molecules that are expressed in cerebellar Purkinje cells with varying degrees of specificity. Here, we show by light microscopic immunocytochemistry and Northern transfer and hybridization that two of these markers, namely, L7 and PEP19, are expressed in the retina of mouse and rabbit, while a third marker, cerebellin, is absent. Light and electron microscopic immunocytochemistry proves that L7-like immunoreactivity is restricted to rod bipolar cells, while PEP 19-like immunoreactivity is distributed in both rod and cone bipolars. PEP19 is also expressed by subsets of amacrine and ganglion cells. The density of PEP19-positive bipolar cells is greater than that of L7-positive bipolar cells, although the density of each is approximately equal in central and peripheral portions of the retina. An antiserum to a fourth Purkinje cell marker, vitamin D-dependent calcium-binding protein-28 kD (CaBP), reveals primarily axonless horizontal cells, but also subsets of rod bipolar, amacrine, and, in the mouse but not in the rabbit, ganglion cells. The processes of immunoreactive cell bodies form discrete bands in the internal plexiform layer, and mixtures of the antisera help distinguish their identity. Thus, these Purkinje cell markers can be used at the electron microscopic level to unravel the extremely complex neuropil of this retinal layer. Furthermore, knowledge of the retinal distribution of this panel of molecules is of general value for future studies of retinal neuronal typology and can serve to map the densities of subsets of bipolar cells throughout the retina. The expression of L7 and PEP19 in bipolar cells and in Purkinje cells suggests a biochemical relationship between these two spatially distant neuronal populations.

Animals↗
PubMed1991

Precerebellin is a cerebellum-specific protein with similarity to the globular domain of complement C1q B chain.

The cerebellum contains a hexadecapeptide, termed cerebellin, that is conserved in sequence from human to chicken. Three independent, overlapping cDNA clones have been isolated from a human cerebellum cDNA library that encode the cerebellin sequence. The longest clone codes for a protein of 193 amino acids that we term precerebellin. This protein has a significant similarity (31.3% identity, 52.2% similarity) to the globular (non-collagen-like) region of the B chain of human complement component C1q. The region of relatedness extends over approximately 145 amino acids located in the carboxyl terminus of both proteins. Unlike C1q B chain, no collagen-like motifs are present in the amino-terminal regions of precerebellin. The amino terminus of precerebellin contains three possible N-linked glycosylation sites. Although hydrophobic amino acids are clustered at the amino terminus, they do not conform to the classical signal-peptide motif, and no other obvious membrane-spanning domains are predicted from the cDNA sequence. The cDNA predicts that the cerebellin peptide is flanked by Val-Arg and Glu-Pro residues. Therefore, cerebellin is not liberated from precerebellin by the classical dibasic amino acid proteolytic-cleavage mechanism seen in many neuropeptide precursors. In Northern (RNA) blots, precerebellin transcripts, with four distinct sizes (1.8, 2.3, 2.7, and 3.0 kilobases), are abundant in cerebellum. These transcripts are present at either very low or undetectable levels in other brain areas and extraneural structures. A similar pattern of cerebellin precursor transcripts are seen in rat, mouse, and human cerebellum. Furthermore, a partial genomic fragment from mouse shows the same bands in Northern blots as the human cDNA clone. During rat development, precerebellin transcripts mirror the level of cerebellin peptide. Low levels of precerebellin mRNA are seen at birth. Levels increase modestly from postpartum day 1 to 8, then increase more dramatically between day 5 and 15, and eventually reach peak values between day 21 and 56. Because cerebellin-like immunoreactivity is associated with Purkinje cell postsynaptic structures, these data raise interesting possibilities concerning the function of the cerebellin precursor in synaptic physiology.

Amino Acid Sequence↗
PubMed1991

Proto-oncogene transcription factors and epilepsy.

Chemically and electrically induced seizures elicit the rapid transcriptional activation in neurons of a class of genes referred to as cellular immediate-early genes. Since the products of these genes include transcription factors and cytokines, they are proposed to be involved in coupling neuronal excitation to a complex, and poorly understood, programme of cellular responses that involves the regulation of gene expression. Products of two cellular immediate-early genes, c-fos and c-jun, are components of the transcription factor AP-1. In this review, Jim Morgan and Tom Curran discuss how these gene products have begun to reveal some of the molecular details of stimulus-transcription coupling in the nervous system following seizures. In addition, these genes have provided novel reagents and concepts for investigating the biochemical and cellular sequelae of seizure in the CNS, and point towards new avenues of research and potential therapeutic targets in epilepsy.

Animals↗
PubMed1991

Identification of a new non-neuronal cell type in rat olfactory epithelium.

We have examined adult and embryonic rat olfactory epithelia by immunohistochemical techniques using the monoclonal antibody 1A-6, which was raised against embryonic rat olfactory epithelia. A heretofore unidentified cell type, reactive with the monoclonal antibody 1A-6, was observed scattered within the epithelium. The 1A-6 reactivity of these cells is most intense on the microvilli projecting from the luminal cell surfaces. For several reasons, we believe these cells are not neurons but a distinct subpopulation of supporting cells or some other sort of non-neuronal cells. (1) They have no identifiable axonal process, are not reactive with an antibody against olfactory marker protein, and are not in juxtaposition with trigeminal axons. (2) They survive ablation of the olfactory bulb. (3) Their nuclei lie within the supporting cell layer, and they resemble supporting cells morphologically and in their [3H]thymidine birthdating and turnover characteristics. However, the 1A-6-positive cells fail to react with the general supporting cell-specific monoclonal antibody SUS-1 [see Hempstead J. L. and Morgan J. I. (1983) Brain Res. 188, 289-295] a finding which suggests that they are not typical supporting cells. Immunoreactivity to 1A-6 is developmentally regulated. Immunohistochemical preparations of almost all tissues we examined showed widespread reactivity in the embryo but a much more restricted pattern in the adult. In the olfactory epithelium of the fetus, the luminal surfaces of all cells, including supporting cells and olfactory receptor cells and cilia, are reactive, while in the adult only the non-neuronal cell subpopulation shows this reactivity. We also found that during the reconstitution of olfactory epithelium which occurs in response to olfactory bulbectomy-induced neuronal degeneration, fetal patterns of 1A-6 reactivity are not re-expressed, i.e. the only 1A-6-positive cells are the non-neuronal cells seen in unperturbed adult olfactory epithelium. Preliminary biochemical analyses of membrane fractions from E19 brain and from adult olfactory mucosa indicate that the 1A-6 reactivity is associated with two bands, having molecular weights of 42,000 and 46,000 on Western blots.

Age Factors↗
PubMed1991

Electrical activity in cerebellar cultures determines Purkinje cell dendritic growth patterns.

In primary dissociated cultures of mouse cerebellum a number of Purkinje cell-specific marker proteins and characteristic ionic currents appear at the appropriate developmental time. During the first week after plating, Purkinje cell dendrites elongate, but as electrical activity emerges the dendrites stop growing and branch. If endogenous electrical activity is inhibited by chronic tetrodotoxin or high magnesium treatment, dendrites continue to elongate, as if they were still immature. At the time that branching begins, intracellular calcium levels become sensitive to tetrodotoxin, suggesting that this cation may be involved in dendrite growth. Even apparently mature Purkinje cells alter their dendritic growth in response to changes in activity, suggesting long-term plasticity.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1991

Developmental regulation of beta-thymosins in the rat central nervous system.

HPLC analysis of guanidinium hydrochloride extracts of neonatal and adult rat brain revealed a polypeptide that is present in high concentration in the immature nervous system, but whose levels decline dramatically in the adult. This polypeptide has been isolated and its complete amino acid sequence determined by gas-phase Edman degradation following specific chemical and enzymatic cleavages. The molecule is identified as thymosin beta 10, a member of a multigene family that encodes a structurally conserved series of small acidic polypeptides of uncertain function. Thymosin beta 10 is present in the developing nervous system as early as embryonic day 9. Levels subsequently increase to peak values between embryonic day 15 and postpartum day 3, before falling to adult values (about a 20-fold reduction) by postpartum day 14. The elevated levels of thymosin beta 10 in fetal and neonatal brain correlate with high levels of thymosin beta 10 mRNA, whereas the low values of the polypeptide in the adult and juvenile are mirrored by an approximate 15-fold reduction in specific mRNA. In comparison, the levels of thymosin beta 4 polypeptide, a homologue of thymosin beta 10, only decline by about 20% during the same developmental period. However, the mRNA encoding thymosin beta 4 is elevated in fetal brain, and its levels decrease approximately four-fold to a stable value around the time of birth. The reason for this discrepancy between thymosin beta 4 protein and mRNA levels is unknown. Thymosin beta 10 can also be detected by HPLC in fetal liver, where levels are approximately 5% of those in brain. In liver, thymosin beta 10 also declines following birth. It is concluded that beta-thymosin expression (as measured by steady-state mRNA and polypeptide levels) is both up- and down-regulated during different phases of maturation of the mammalian nervous system.

Aging↗
PubMed1991

Retinoic acid regulates thymosin beta 10 levels in rat neuroblastoma cells.

A small acidic polypeptide, termed thymosin beta 10, has been identified and is present in the nervous system of the rat by the ninth day of gestation. Thymosin beta 10 levels rise during the remaining days of life in utero, and then decline to nearly undetectable values between the second and fourth week post partum. The present study investigates the possible developmental signals and mechanisms that might regulate the expression of thymosin beta 10 during neuroembryogenesis. Many cell lines derived from tumors of the central nervous system express thymosin beta 10, as well as its homologue gene product, thymosin beta 4. Because some of these cell lines respond to exogenously applied agents by increasing their apparent state of differentiation, we have determined whether thymosin beta 10 levels are coordinately modulated. In several neuroblastomas, including the B103 and B104 lines, retinoic acid elicits a time- and dose-dependent increase in the content of thymosin beta 10, but not that of thymosin beta 4. The increase in thymosin beta 10 polypeptide is associated with a marked increase in the specific mRNA encoding this molecule. The mRNA for thymosin beta 4 is unaffected by retinoic acid. This is in contrast with the situation in vivo, where the expression of both genes decreases after birth. Other agents that influence the morphology of B104 cells, such as phorbol esters and dibutyryl cyclic AMP, have no influence on beta-thymosin levels. A range of steroids, which like retinoids act upon nuclear receptors, was also inactive. The stimulatory action of retinoic acid is detectable within 4 h, and thymosin beta 10 peptide levels continue to rise for at least 4 days. The influence of the isoprenoid is fully reversible and exhibits structural specificity. We believe that this culture system is mimicking the early rising phase of thymosin beta 10 levels in brain and that endogenous retinoids may be candidate physiological regulators of this gene.

Animals↗
PubMed1990

A promoter that drives transgene expression in cerebellar Purkinje and retinal bipolar neurons.

A genomic clone encoding the Purkinje cell-specific L7 protein has been isolated and utilized to drive the expression of beta-galactosidase in mice. Three independent transgenic lines, germ line transformed with an L7-beta-galactosidase fusion gene, exhibit beta-galactosidase expression in both cerebellar Purkinje cells and retinal bipolar neurons. This distribution is the same as that previously determined for the L7 protein by immunohistochemistry. The transgenic murine lines can be used to obtain populations of marked Purkinje and bipolar neurons. Similar L7 promoter constructs can be used to express other foreign genes specifically in these two classes of neurons.

Animals↗