Biomedical subjects

I Delalle

Publications and source records attributed to I Delalle.

10 recordsLinked to original sources

PubMed2000

The adhesion signaling molecule p190 RhoGAP is required for morphogenetic processes in neural development.

Rho GTPases direct actin rearrangements in response to a variety of extracellular signals. P190 RhoGAP (GTPase activating protein) is a potent Rho regulator that mediates integrin-dependent adhesion signaling in cultured cells. We have determined that p190 RhoGAP is specifically expressed at high levels throughout the developing nervous system. Mice lacking functional p190 RhoGAP exhibit several defects in neural development that are reminiscent of those described in mice lacking certain mediators of neural cell adhesion. The defects reflect aberrant tissue morphogenesis and include abnormalities in forebrain hemisphere fusion, ventricle shape, optic cup formation, neural tube closure, and layering of the cerebral cortex. In cells of the neural tube floor plate of p190 RhoGAP mutant mice, polymerized actin accumulates excessively, suggesting a role for p190 RhoGAP in the regulation of +Rho-mediated actin assembly within the neuroepithelium. Significantly, several of the observed tissue fusion defects seen in the mutant mice are also found in mice lacking MARCKS, the major substrate of protein kinase C (PKC), and we have found that p190 RhoGAP is also a PKC substrate in vivo. Upon either direct activation of PKC or in response to integrin engagement, p190 RhoGAP is rapidly translocated to regions of membrane ruffling, where it colocalizes with polymerized actin. Together, these results suggest that upon activation of neural adhesion molecules, the action of PKC and p190 RhoGAP leads to a modulation of Rho GTPase activity to direct several actin-dependent morphogenetic processes required for normal neural development.

Alleles↗

PubMed1999

Cyclin E-p27 opposition and regulation of the G1 phase of the cell cycle in the murine neocortical PVE: a quantitative analysis of mRNA in situ hybridization.

We have analyzed the expression patterns of mRNAs of five cell cycle related proteins in the ventricular zone of the neocortical cerebral wall over the course of the neuronogenetic interval in the mouse. One set of mRNAs (cyclin E and p21) are initially expressed at high levels but expression then falls to a low asymptote. A second set (p27, cyclin B and cdk2) are initially expressed at low levels but ascend to peak levels only to decline again. These patterns divide the overall neuronogenetic interval into three phases. In phase 1 cyclin E and p21 levels of mRNA expression are high, while those of mRNAs of p27, cdk2 and cyclin B are low. In this phase the fraction of cells leaving the cycle after each mitosis, Q, is low and the duration of the G1 phase, TG1, is short. In phase 2 levels of expression of cyclin E and p21 fall to asymptote while levels of expression of mRNA of the other three proteins reach their peaks. Q increases to approach 0.5 and TG1 increases even more rapidly to approach its maximum length. In phase 3 levels of expression of cyclin E and p21 mRNAs remain low and those of the mRNAs of the other three proteins fall. TG1 becomes maximum and Q rapidly increases to 1.0. The character of these phases can be understood in part as consequences of the reciprocal regulatory influence of p27 and cyclin E and of the rate limiting functions of p27 at the restriction point and of cyclin E at the G1 to S transition.

Animals↗

PubMed1997

Laminar distribution of neuropeptide Y-immunoreactive neurons in human prefrontal cortex during development.

Neuropeptide Y (NPY) is present in neurons of the adult human cerebral cortex. In view of the reported roles of NPY in the central nervous system in health and during certain disease conditions, we have studied normal development of NPY immunoreactivity (-ir) in the human prefrontal cortex (PFC), Brodmann areas 9 and 46. Twenty-six specimens ranging from the ages of 14 postovulatory weeks to 34 years exhibited patterns that revealed six periods in the development of the laminar distribution and density of NPY-ir neurons. Changes during prenatal and perinatal periods reflect the onset, development, and resolution of the transient fetal telencephalic compartments, including the subplate zone, in which NPY-ir neurons are especially abundant. Before the age of 1 year, the majority of NPY-ir neurons were found in the subplate zone, whereas, after 1 year, the majority were seen in the cortical layers. This is in contrast with the human visual cortex, where the majority of NPY-ir neurons were still located in the white matter. The density of cortical NPY-ir neurons increased in the fifth developmental period (ages 4-7 years), coinciding with the increase of cortical volume and marked progression of cognitive functions. The adult pattern of a relatively low density of cortical NPY-ir neurons was reached in period 6 (from about 8 years), when individual variation also became apparent. Our data point to a protracted maturation of NPY-ir in the human PFC and to different distribution patterns of NPY-ir neurons in different cortical areas.

Adolescent↗

PubMed1997

Morphology of neuropeptide Y-immunoreactive neurons and fibers in human prefrontal cortex during prenatal and postnatal development.

The subplate and marginal zone are prominent transient zones of the developing cerebral wall and contain a variety of neuropeptide Y-immunoreactive (NPY-ir) cells. This study investigates morphological maturation as well as regression and/or transformation of NPY-ir neurons in the transient compartments and the cortical plate of the human frontal cortex. The most prominent NPY-ir neuronal population is that of NPY-ir subplate neurons. They exhibited features of all subplate neuronal types reported in Golgi-impregnated sections, with the exception of the pyramidal type. The NPY-ir subplate neurons were the largest of all NPY-ir neurons, but their size regressed rather sharply between 1 month after birth and 2 years. In the NPY-ir subplate neurons and in the NPY-ir Cajal-Retzius cells of the marginal zone, signs of degeneration were observed between 36 postovulatory weeks and about 9 months after birth. Only a few subpial granular layer cells were NPY positive, and they exhibited degeneration-like features, such as cytoplasmic vacuolization, as early as 23 postovulatory weeks. However, NPY-ir neurons continued to be present in the adult counterparts of the subplate and marginal zone, i.e., gyral white matter and layer I, respectively. Across cortical layers II-VI, NPY-ir neurons had the hallmarks of all aspinous short-axon types, with the exception of the neurogliaform and the chandelier neuronal types. Some signs of degeneration were also observed among a few cortical NPY-ir neurons around birth. Unlike the NPY-ir subplate neurons, the general development of cortical NPY-ir neurons did not show an obvious decline in neuronal size and was similar to the pattern in Golgi-staining.

Adolescent↗

PubMed1997

Temporal and spatial patterns of expression of p35, a regulatory subunit of cyclin-dependent kinase 5, in the nervous system of the mouse.

The protein p35 is a regulatory subunit of cyclin-dependent kinase 5. It has no recognized homology to cyclins but binds to and activates cyclin-dependent kinase 5 directly in the absence of other protein molecules. Cyclin-dependent kinase 5 was initially isolated by homology to the key cell cycle regulator cdc2 kinase and later identified as a neuronal kinase that phosphorylates histone H1, tau or neurofilaments. This kinase is localized in axons of the developing and mature nervous system. To understand the role of p35 as a regulator of cyclin-dependent kinase 5 activity in the CNS, we examined the pattern of expression of p35 mRNA in the nervous system of embryonic, early postnatal and adult mice. In separate experiments, we also examined the spatial distribution of cyclin-dependent kinase 5 mRNA and the activity of cyclin-dependent kinase 5/p35 kinase complex. Postmitotic cells express p35 mRNA immediately after they leave the zones of cell proliferation. It is also expressed in developing axonal tracts in the brain. Cyclin-dependent kinase 5 mRNA is present in postmitotic and in proliferative cells throughout the embryonic central nervous system. During early postnatal period signal for p35 mRNA declines while that for cyclin-dependent kinase 5 mRNA increases throughout the brain. In the adult brain although both p35 and cyclin-dependent kinase 5 mRNAs are expressed at relatively high levels in certain structures associated with the limbic system, considerable differences exist in the patterns of their distribution in other parts of the brain. These data suggest that the p35/cyclin-dependent kinase 5 complex may be associated with early events of neuronal development such as neuronal migration and axonal growth while in the limbic system of the mature brain it may be associated with the maintenance of neuronal plasticity.

Aging↗

PubMed1996

Regulation of normal proliferation in the developing cerebrum potential actions of trophic factors.

We review here a computational model of neocortical histogenesis based upon experiments in the developing cerebral wall of the mouse. Though based upon experiments in mouse, commonalities of developmental history and structure of neocortex across mammalian species suggest that the principles which support this model will be generally applicable to neocortical evolution and development across species. In its scope the model spans the successive histogenetic events: cell proliferation, cell migration, and the positioning of cell somata in neocortical layers following migration. Neurons are produced in a pseudostratified epithelium (PVE) which lines the ventricular cavaties of the embryonic cerebrum. The parameters which determine the rate and total number of neurons produced in the PVE are (1) the size of the founder population, (2) the number of integer cell cycles executed by the founder population and its progeny in the course of the neuronogenetic interval, (3) the growth fraction, and (4) the fraction of cells which exits the cycle (Q fraction) with each integer cycle. There is a systematic relationship between the integer cycle of origin and the sequence of cell migration, position in the cortex, and the extent to which a set of postmigratory neurons will be diluted in the cortex by the combined effects of tissue growth and cell death. Variation across species in the number of integer cell cycles as a function of the rate of progression of Q may be expected to modulate profoundly the total numbers of neurons that are produced but not the relative proportions of neurons assigned to the major neocortical layers.

Animals↗

PubMed1994

p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5.

Cyclin-dependent kinase 5 (Cdk5) was originally isolated through its structural homology to human Cdc2, a key regulator of cell-cycle progression. In tissue samples from adult mice, Cdk5 protein is found at the highest level in brain, at an intermediate level in testis, and at low or undetectable levels in all other tissues, but brain is the only tissue that shows Cdk5 histone H1 kinase activity. No equivalent kinase activity has been found in tissue culture cell lines despite high levels of Cdk5. This raised the possibility that a Cdk5 regulatory subunit was responsible for the activation of Cdk5 in brain. Here we describe the cloning and characterization of a regulatory subunit for Cdk5 known as p35. p35 displays a neuronal cell-specific pattern of expression, it associates physically with Cdk5 in vivo and activates the Cdk5 kinase. p35 differs from the mammalian cyclins and thus represents a new type of regulatory subunit for cyclin-dependent kinase activity.

Amino Acid Sequence↗

PubMed1991

Prenatal and perinatal development of the somatostatin-immunoreactive neurons in the human prefrontal cortex.

The earliest somatostatin-immunoreactive (SS-Ir) perikarya of the human fetal frontal cortex appear in the transient subplate zone at 22 weeks of gestation. Around 32 weeks of gestation there is an increase in the number of SS-Ir neurons at the interface between the subplate zone and the cortical plate. The newborn-cortex shows decline in the overall number of SS-Ir neurons parallel to the appearance of SS-Ir neurons in the superficial layers. In conclusion, the subplate neurons are the source of the earliest peptidergic activity in the cortex. Furthermore, the distribution and density of peptidergic neurons undergo significant reorganization during the perinatal development.

Cerebral Cortex↗

PubMed1991

Zagreb research collection of human brains for developmental neurobiologists and clinical neuroscientists.

The aim of this paper was to offer for the first time a selective and systematic description of the "Zabreb Neuroembryological Collection" of human brains and to illustrate the major results of our research team. Throughout these 16 years of continuous and systematic research, we have applied different techniques for demonstrating the cytoarchitectonics (Nissl staining), neuronal morphology (Golgi impregnation), synaptogenesis (EM analysis), growing pathways (acetylcholinesterase histochemistry) and transmitter-related properties of developing neuronal populations (immunocytochemistry and acetylcholinesterase histochemistry) on several hundred human brains ranging in age from the 5th week post-conception to 90 years. The combination of classical and modern research techniques applied to the constantly growing developmental collection, as well as the continuous evaluation of our data in the light of experimental work in non-human primates, has led to the discovery of an early synaptogenesis within the human cortical anlage and hitherto undescribed transient subplate zone; our results also provided the first comprehensive evidence concerning the timing and pattern of development of afferent fiber systems in the human cortex. All this enabled us to offer a well-documented and coherent reconstruction of major histogenetic events in the human brain. We concluded that structural remodeling and reorganization of the brain, from the transient patterns of the fetal organization through the postnatal phase of transient overproduction of circuitry elements to the final maturation, is the crucial principle of development. Fetal neuronal elements (afferents, synapses and postsynaptic neurons) display transient patterns of laminar, vertical and modular organization and transient cellular interactions and competition in the subplate zone are crucial for the formation of cortical connections. The elucidation of the nature and timing of these histogenetic reorganizational events in the human brain represents the first step towards determining the neurobiological basis of the emergence of behavior, neural functions and cognition in human fetuses, infants and children, which takes place during perinatal and early postnatal life.

Acetylcholinesterase↗

PubMedDate not supplied

[Terrorist explosions--medical aspects].

In this paper we present the review of medical and organizational aspects of terroristic explosion as a type of urban disaster. We have focused on consequences of the explosion of unfragmented explosive devices, particularly regarding the type and localization of injuries. The definitions of urban disaster is given and organizational problems in these situations are classified.

Explosions↗