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PubMed2005

Large-scale maintenance of dual projections by callosal and frontal cortical projection neurons in adult mice.

Integration of sensory-motor information in premotor cortex of rodents occurs largely through callosal and frontal cortical association projections directed in a hierarchically organized manner. Although most anatomical studies in rodents have been performed in rats, mammalian genetic models have focused on mice, because of their successful manipulation on the genetic and cell biological levels. It is therefore important to establish the normal patterns of anatomical connectivity in mice, which potentially differ from those in rats. The goal of this study is to investigate the anatomical development of callosal and frontal premotor projection neurons (CPN and FPN, respectively) in mouse sensory-motor and premotor cortex and to investigate quantitatively the potential laminar differences between these neurons with simultaneous callosal and frontal projections during development. The retrograde tracers Fluoro-Gold and DiI were injected into sensory-motor and premotor cortices, respectively, C57Bl/6 mice at different developmental times (P2, P8, P21, adult). We found that, in contrast to the case in primate and cat, there is widespread overlap in populations of long-distance projection neurons in mice; many projection neurons have simultaneous projections to both contralateral somatosensory cortex and ipsilateral frontal cortex, and a considerable number of these dual projections persist into adulthood. In addition, there are significant laminar differences in the percentage of neurons with simultaneous callosal and frontal projections, and an isolated population of layer V FPN has bilateral projections to both premotor cortical hemispheres. Taken together, our results indicate that a large proportion of individual projection neurons maintains simultaneous callosal and frontal projections in adult mice, suggesting that these dual projections might serve the critical function of integrating motor coordination information with multimodal association areas.

Animals↗
PubMed1984

Torpedo electromotor system development: a quantitative analysis of synaptogenesis.

Synaptogenesis in the electric organ of Torpedo marmorato has been studied quantitatively at the ultrastructural level of observation. In addition to establishing the normal developmental time course for this event we were interested in determining whether a gradient of synaptogenesis might be present because the electric organ produces several morphologically recognizable spatiotemporal gradients during its early ontogeny. These gradients genesis of electrocyte columns, both gradients of which are operative for periods of weeks. No gradient of synaptogenesis was found, indicating this to be a synchronous process. The idea is advanced that synaptogenesis in the electric organ is modulated by extrinsic influences, many of which may originate from the target electrocytes which, by this time, have become synchronized in their development.

Acetylcholinesterase↗
PubMed1991

Pattern formation in the striatum: neurons with early projections to the substantia nigra survive the cell death period.

During the early postnatal period the striatum undergoes significant cell death. The specificity and regulation of this regressive event may be particularly interesting in the light of recent findings demonstrating that a developmentally organized compartmental architecture exists in the striatum. The striatum can be divided into two complementary and phenotypically distinct compartments, the patches and the matrix. In the adult, these two striatal compartments can be distinguished on the basis of their anatomy and a series of compartment-specific biochemical and hodological markers. We have previously demonstrated that the neurons within the patch and matrix compartments become postmitotic and make connections with the substantia nigra at distinct and sequential developmental times. The majority of patch neurons become postmitotic between embryonic days 12 and 15 and make a striatonigral connection prenatally. In contrast, a majority of matrix neurons become postmitotic between embryonic days 17 and 20 and do not form an efferent connection to the substantia nigra until the first postnatal week. Here we investigated whether either neuronal birthdate or time of making an efferent projection correlates with a neuron's probability of surviving the cell death period. We found that both the patch and matrix compartments undergo their entire cell death period by the end of the first postnatal week. During this period approximately 30% of striatal neurons are subject to cell death, regardless of striatal compartment. Neuronal counts within the striatal patch compartment suggest that both early born neurons (embryonic day 13) and early projecting neurons (to the substantia nigra) are preferentially spared. However, their considerable overlap (i.e., most early born neurons also have a nigral projection) prevents assessment of which feature is critical for survival. In contrast, there are small, but mostly separate, populations of early born and early projecting neurons within the matrix compartment. Quantitative analysis of these two distinct populations suggests that while early projection neurons within the matrix are spared, the early born matrix neurons lacking an early nigral projection undergo significant cell death. This proposal is further supported by the observation that the percentage of early born neurons in both the patch and matrix compartments that also have an early nigral projection increases from postnatal day 2 to 17. This finding suggests that among the early born striatal neurons in both compartments, those that do not project to the nigra selectively die during the cell death period. Together these results support the hypothesis that completion of an early projection to the substantia nigra gives neurons an advantage for surviving the cell death period.

Animals↗
PubMed1991

Adrenal steroids regulate postnatal development of the rat dentate gyrus: II. Effects of glucocorticoids and mineralocorticoids on cell birth.

Unlike the majority of mammalian brain regions, the rat dentate gyrus undergoes maximal cell birth and cell death during the same developmental time period. Granule cell birth and death peak at the end of the first postnatal week. We have found that manipulations of glucocorticoid levels during the stress hyporesponsive period profoundly influence the density of pyknotic cells in the dentate gyrus while apparently not affecting the density of healthy cells. This raises the possibility that glucocorticoids are regulating processes in addition to cell death, i.e., cell birth. In order to determine whether increases in circulating glucocorticoids or mineralocorticoids affect the birth of cells in the developing dentate gyrus, 3H-thymidine autoradiography was performed on brains of rat pups treated with either corticosterone or aldosterone during the first postnatal week. Quantitative analysis of 3H-thymidine-labelled cells revealed significant decreases in the density of labelled cells in the granule cell layers with both corticosterone and aldosterone treatment. In these same brains, significant decreases in the density of pyknotic cells were also observed in the granule cell layers. However, no changes in the numbers of 3H-thymidine-labelled pyknotic cells were observed with any treatment. Increases in circulating corticosterone or aldosterone resulted in significant increases in the density of both 3H-thymidine-labelled and pyknotic cells in the hilus. These results suggest that dentate gyrus cell birth and cell death are related and that these processes are regulated by adrenal steroids.

Adrenal Cortex Hormones↗
PubMed1991

Postnatal development of cholinergic markers in the rat olfactory bulb: a histochemical and immunocytochemical study.

The present study has defined the developmental time course and the distribution patterns of neuronal fibers and cell bodies displaying acetylcholinesterase (AChE) activity or choline acetyltransferase (ChAT) immunoreactivity in the rat olfactory bulb. The results indicate that the deployment of centrifugal AChE-containing fibers is essentially postnatal. The subset of atypical glomeruli, including the modified glomerular complex, is innervated as early as the first postnatal day while the normal ones are not reached by this type of afferent before postnatal day 6. The comparison of AChE labelling with ChAT immunoreactivity strongly supports the assumption that AChE-containing fibers represent mainly, if not exclusively, the cholinergic bulbopetal innervation emanating from the basal forebrain. A quantitative study has confirmed that the density of labelled fibers increases gradually in the postnatal period and spreads heterogeneously among the bulbar layers. The selective precocious innervation of atypical glomeruli is in favor of their involvement in the early processing of olfactory information in the olfactory bulb. Acetylcholinesterase is also expressed within a subset of ChAT-negative interneurons of the developing olfactory bulb. The number of neurons expressing AChE increases from birth to postnatal day 15 and then decreases to reach the adult value on about postnatal day 30. This neuronal population could constitute a cholinoceptive subset mediating the effects of cholinergic afferents on the bulbar neuronal network.

Acetylcholinesterase↗
PubMed1995

Distribution and developmental expression of octopamine-immunoreactive neurons in the central nervous system of the leech.

Octopamine, a biogenic amine analogous to norepinephrine, plays an important role in the orchestration and modulation of invertebrate behavior. In the leech, the behavioral actions of octopamine have been demonstrated; however, identification of octopaminergic neurons had not been determined by using immunohistochemical techniques. Thus, we used an antibody highly specific to octopamine to examine the distribution of octopamine-immunoreactive neurons in the segmental ganglia of American and European medicinal leeches (Macrobdella decora and Hirudo medicinalis). One pair of octopamine-immunoreactive neurons was located in the dorsolateral ganglionic region of anterior ganglia 1-6 and posterior ganglia 15-21. No corresponding octopamine-immunoreactive neurons were found in midbody ganglia 7-14. Using Neutral Red staining in combination with intracellular Neurobiotin injections and octopamine immunostaining, we determined the identity of the dorsolateral octopamine-immunoreactive cells. The dorsolateral octopamine-immunoreactive neuron (the DLO) was not cell 21, the only previously reported Neutral Red staining neuron in the dorsolateral position. We also determined that the Leydig neuron was not octopamine immunoreactive in either of the two medicinal leech species. Octopamine immunostaining in the sex ganglia revealed hundreds of immunoreactive neurons in sexually mature leeches. Such neurons were not observed in juvenile leeches. The developmental time course of octopamine immunoreactivity in the dorsolateral octopamine-immunoreactive neurons was also investigated by staining embryonic Hirudo medicinalis. Octopamine expression occurred relatively late as compared with the detectable onset of serotonin expression. Octopamine expression in the dorsolateral octopamine-immunoreactive cells was not detectable at early to mid-embryonic stages, and must commence during late embryonic to early juvenile stages. The identification of octopamine-immunoreactive cells now sets the stage for further investigations into the functional role of octopamine in leech behavior and the development of behavior.

Animals↗
PubMed2005

Multiple sensitive periods in human visual development: evidence from visually deprived children.

Psychophysical studies of children deprived of early visual experience by dense cataracts indicate that there are multiple sensitive periods during which experience can influence visual development. We note three sensitive periods within acuity, each with different developmental time courses: the period of visually-driven normal development, the sensitive period for damage, and the sensitive period for recovery. Moreover, there are different sensitive periods for different aspects of vision. Relative to the period of visually driven normal development, the sensitive period for damage is surprisingly long for acuity, peripheral vision, and asymmetry of optokinetic nystagmus, but surprisingly short for global motion. A comparison of results from unilaterally versus bilaterally deprived children provides insights into the complex nature of interactions between the eyes during normal visual development.

Adolescent↗
PubMed2004

Cellular growth and rearrangement during the development of the mammalian organ of Corti.

The sensory epithelium of the mammalian cochlea, the organ of Corti, is comprised of ordered rows of cells, including inner and outer hair cells. Recent results suggest that physical changes in the overall size and shape of the cochlear duct, including possible convergence and extension, could play a role in the development of this pattern. To examine this hypothesis, changes in cell size and distribution were determined for different regions of the cochlea duct during embryonic development. In addition, changes in the spatial distribution of sensory precursor cells were determined at different developmental time points based on expression of p27kip1. Unique changes in luminal surface area, cell density, and number of cell contacts were observed for each region of the duct. Moreover, the spatial distribution of p27kip1-positive cells changed from short and broad early in development, to long and narrow. These results are consistent with the hypothesis that convergence and extension plays a role in cellular patterning within the organ of Corti.

Animals↗
PubMed1988

A comparison of high frequency switching in the yeast Candida albicans and the slime mold Dictyostelium discoideum.

Recently, high frequency switching systems have been identified in the infectious yeast Candida albicans and the cellular slime mold Dictyostelium discoideum. In C. albicans, cells can switch at spontaneous frequencies as high as 10(-2) between seven general colony morphologies in the case of strain 3153A or between two major phenotypes in the white-opaque transition in strain WO-1. In the latter system, dramatic changes occur in cellular phenotype as well. In D. discoideum, cells can switch at spontaneous frequencies of roughly 10(-2) between a number of colony phenotypes which include alterations in developmental timing, blocks at particular morphogenetic stages, morphological aberrations, and aggregation-minus. In the C. albicans and D. discoideum switching systems, the following characteristics are shared: 1) a limited number of switch phenotypes; 2) heritability; 3) high frequency reversibility; 4) low and high frequency modes of switching; and 5) ultraviolet (UV) stimulation of switching of cells in a low frequency mode of switching.

Candida albicans↗
PubMed1992

Selection of murine T cell receptor alpha beta and gamma delta cells in organ cultures established from 14-day embryos.

The expression of minor lymphocyte stimulatory locus (Mls) determinants in combination with murine major histocompatibility complex (MHC) class II molecules, leads to the destruction of lymphocytes bearing specific V region-encoded T cell receptor (TcR) products. A much studied example is the elimination of V beta 6+ cells in IE+/Mls-1a mice, in which deletion can be detected 7-10 days after birth but is not fully operational earlier in embryonic life. Here we investigate this transitional period in development and show that selective deletion of V beta 6 occurs in vitro, approximately 1 week after organ cultures are established from 14 day embryos. These unmanipulated organ cultures receive no additional cell immigrants after day 14, suggesting that the cellular elements mediating negative selection (or their direct precursors), are already resident in the fetal thymus by day 14 of gestation. Hence, the developmental timing of the outset of rigorous negative selection of V beta 6 is not dictated by the postnatal entry of deleting elements into the thymus, but perhaps by the maturation of the pre-existing environment. Using a parallel organ-culture approach we have looked at the development of V delta 4 and V gamma 3, TcR gamma delta+ cells in a variety of mouse strains. These receptors have recently been reported to be subject of MHC and non-MHC linked selection, respectively. We find that after an initial period of expansion, the number of V gamma 3-expressing cells dramatically declines. However, this selective loss of V gamma 3 cells is not contingent on the C57BL/6 mouse strain (in contrast to a previous report). These findings are discussed in the context of current models of ontogeny and repertoire selection.

Animals↗
PubMed2003

What cardiovascular defect does my prenatal mouse mutant have, and why?

Since the advent of mouse targeted mutations, gene traps, an escalating use of a variety of complex transgenic manipulations, and large-scale chemical mutagenesis projects yielding many mutants with cardiovascular defects, it has become increasingly evident that defects within the heart and vascular system are largely responsible for the observed in utero lethality of the embryo and early fetus. If a transgenically altered embryo survives implantation but fails to be born, it usually indicates that there is some form of lethal cardiovascular defect present. A number of embryonic organ and body systems, including the central nervous system, gut, lungs, urogenital system, and musculoskeletal system appear to have little or no survival value in utero (Copp, 1995). Cardiovascular abnormalities include the failure to establish an adequate yolk-sac vascular circulation, which results in early lethality (E8.5-10.5); poor cardiac function (E9.0-birth); failure to undergo correct looping and chamber formation of the primitive heart tube (E9.0-11.0); improper septation, including division of the common ventricle and atria and the establishment of a divided outflow tract (E11.0-13.0); inadequate establishment of the cardiac conduction system (E12.0-birth); and the failure of the in utero cardiovascular system to adapt to adult life (birth) and close the interatrial and aorta-pulmonary trunk shunts that are required for normal fetal life. Importantly, the developmental timing of lethality is usually a good indicator of both the type of the cardiovascular defect present and may also suggest the possible underlying cause/s. The purpose of this review is both to review the literature and to provide a beginner's guide for analysing cardiovascular defects in mouse mutants.

Animals↗
PubMed2002

Electrophysiological characterization of retinal Müller glial cells from mouse during postnatal development: comparison with rabbit cells.

The electrophysiology of murine Müller cells, and of their precursors, during postnatal development was investigated by using the whole-cell patch-clamp technique. Membrane potential, membrane capacitance, and expression of voltage-gated Na+ currents increased during the first 3 postnatal weeks. During the same period, the membrane resistance decreased due to an upregulation of both inward and outward K+ currents. Glutamate transporter-mediated currents increased during the first postnatal weeks, as well. In Müller (precursor) cells from rabbits, these transporter currents already achieved adult levels at postnatal day 6, the earliest stage studied. Together with the developmental time course of K+ currents, this indicates a delay in the maturation of murine Müller cells, as compared with cells from rabbit.

Aging↗
PubMed1993

Transient presence of GABA in astrocytes of the developing optic nerve.

Immunostaining and high-pressure liquid chromatography (HPLC) were used to study the developmental time course of astrocytic gamma-aminobutyric acid (GABA) expression in rat optic nerve. GABA immunostaining was carried out on cultured astrocytes, and on whole optic nerve. Confocal scanning laser microscopy was used to obtain optical sections in excised whole tissue in order to localize the cellular origins of GABA within the relatively intact optic nerve. GABA immunoreactivity was localized in astrocytes identified by GFAP staining; GABA staining was most intense in early neonatal optic nerve and attenuated over 3 weeks of postnatal development. The staining was pronounced in the astrocyte cell bodies and processes but not in the nucleus. There was a paucity of GABA immunoreactivity by postnatal day 20, both in culture and in whole optic nerve. A biochemical assay for optic nerve GABA using HPLC indicated a relatively high concentration of GABA in the neonate, which rapidly attenuated over the first 3 postnatal weeks. Immunoreactivity for the GABA synthesis enzyme glutamic acid decarboxylase (GAD) was pronounced in neonates but also attenuated with development. These results indicate that GABA and the GABA synthesis enzyme GAD are localized in astrocytes of optic nerve, and that their expression is transient during postnatal development.

Animals↗
PubMed2002

Development of spatial firing in the hippocampus of young rats.

The hippocampal formation participates in learning and memory, particularly that of a spatial nature. In adult rats, individual CA1 pyramidal neurons only fire when the animal visits specific locations in an environment, the "place field" of the neuron. Other structures (postsubiculum, thalamus, cingulum) contain neurons that code for the animal's instantaneous head direction. Previous work has shown that the rat hippocampal formation undergoes anatomical and neurophysiological maturation during the first 2 months of life and that rats <40 days of age are impaired in spatial navigation tasks. Here we show that the locational firing of CA1 pyramidal neurons is both less specific and less stable in animals aged <50 days. However, preliminary results indicate that head directional firing recorded around day 30 is essentially identical to that seen in adult animals. Therefore, the development of reliable, spatially specific place cell activity parallels the developmental time course of spatial navigational ability, but head directional firing appears before full maturation of the hippocampus.

Aging↗
PubMed1984

Pattern of serum protein gene expression in mouse visceral yolk sac and foetal liver.

We have shown by molecular hybridisation that the mRNAs for albumin, transferrin, apolipoprotein-A1, and alpha 1-antitrypsin are expressed at high levels in mouse visceral yolk sac. In contrast, the mRNAs for contrapsin (a plasma protease inhibitor) and the major urinary proteins (MUPs) are not detected in the visceral yolk sac at any stage of embryonic development. Contrapsin and MUP mRNAs both appear late in liver development. These differences in expression suggest that the visceral yolk sac is more similar to the foetal than adult mouse liver in its pattern of gene expression. However, the developmental time course of expression of these mRNAs is different between the foetal liver and the yolk sac. Evidence is also presented that the visceral yolk sac synthesises and secretes other apolipoproteins in addition to apolipoprotein-A1. These results suggest that the visceral yolk sac and foetal liver, two tissues with different embryological lineages, perform similar functions but are independently programmed for expression of the same set of serum protein genes.

Animals↗
PubMed1986

Detection and developmental regulation of the mRNA for the regulatory subunit of the cAMP-dependent protein kinase of D. discoideum by cell-free translation.

cAMP is an important effector of the development of Dictyostelium discoideum amoebae and could exert its effects on gene expression through the cytosolic cAMP-dependent protein kinase (cAK). Antibodies, specific for the regulatory subunit (R) of the cAK, were used to investigate the developmental regulation of the corresponding mRNA (R-mRNA) by in vitro translation and immunoprecipitation. Under such conditions, a single polypeptide of the same mol. wt. as R (42 kd) is detected, showing that the protein is not synthesized as a large precursor. The level of the R-mRNA, which is low in vegetative cells, increases 10- to 20-fold during the first hours of development. Its expression is stimulated by the treatment of AX3 cells with cAMP either added to a concentration of 1 mM or given as 0.1 microM pulses every 5 min, whereas such treatments have little or no effect in cells of strain AX2. The R-mRNA remains highly expressed (0.01-0.03% of translatable mRNA) throughout post-aggregative development; it is not affected by mechanical disaggregation of the multicellular organism. The parallel developmental time courses of the translatable R-mRNA and the R protein produced in vivo suggest that the expression of this polypeptide is regulated at the level of mRNA synthesis.

Carrier Proteins↗
PubMed1986

Cis-acting sequences which regulate expression of the Sgs-4 glue protein gene of Drosophila.

The Sgs-4 glue protein gene of Drosophila is expressed only in third-instar larval salivary glands. Previous work suggests that a regulatory region lies 5' and remote to the gene, as indicated by a region of tissue-specific DNase I hypersensitivity and by underproducing mutants with DNA lesions in the hypersensitive region. Here we demonstrate by germ line transformation of cloned fragments containing Sgs-4 that the sequences between 840 bp 5' and 130 bp 3' to the gene are sufficient for Sgs-4 activity. When 5' sequence was removed to -392, activity was eliminated, thereby verifying the existence of essential sequences far upstream. Fragments that are active include, in addition to the capacity for normal levels of expression, three other cis-acting regulatory activities: developmental timing, tissue specificity, and dosage compensation. In contrast, the fragments tested did not specify formation of the puff with which Sgs-4 is normally associated. As shown by chromosomal rearrangements, the region required for puffing is limited to 16-19 kb surrounding the gene.

Animals↗
PubMed1988

Functional redundancy in the tissue-specific enhancer of the Drosophila Sgs-4 gene.

During the last day of larval development, the Sgs-4 glue gene of Drosophila melanogaster is expressed at high levels in a single tissue, the larval salivary glands. As shown by transformation experiments and by DNA sequence analysis of Sgs-4 underproducing strains, an essential regulatory region for Sgs-4 expression lies between 149 and 568 bp upstream from the transcribed part of the gene. This region shows the positional independence of a transcriptional enhancer and directs at least three regulatory activities: tissue specificity, developmental timing and high-level expression. Here we use a transient transformation assay to identify three elements within this enhancer that are involved in tissue specificity. For at least this regulatory activity the enhancer is internally redundant. Any pairwise combination of the three elements is sufficient to direct salivary gland expression, although none of the three can act alone.

Animals↗