Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “cortical development”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources

Spontaneous calcium transients in developing cortical neurons regulate axon outgrowth.

Growth cones of cortical axons pause for many hours in preparation for axon branching. They become large and complex compared with small advancing growth cones. We wanted to investigate whether calcium transients regulate the advance of mammalian CNS growth cones. We found that spontaneous calcium transients in developing cortical neurons have characteristic patterns, frequencies, and amplitudes. Importantly, neurons with large paused growth cones exhibit high-frequency spontaneous calcium transients, which are rare in those with small advancing growth cones. The incidence, frequencies, and amplitudes of calcium transients are inversely related to rates of axon outgrowth. The transients are mediated primarily by L-type voltage-gated calcium channels, and silencing them with channel blockers promotes axon outgrowth. Thus calcium transients regulate growth cone advance by direct effects on the growth cone.

Animals↗

Demarcation of early mammalian cortical development by differential expression of fringe genes.

Fringe has originally been found in Drosophila as a gene encoding a putative secreted protein which regulates the sensitivity of Notch signaling pathway to different ligands. We show that three members of murine fringe gene family, Lunatic fringe (L-fng), Manic fringe (M-fng) and Radical fringe (R-fng), show related patterns of expression in the developing cerebral wall. L-fng is expressed in immature cells in the ventricular zone. M-fng is upregulated transiently in maturing neurons when they leave the ventricular zone (VZ). R-fng is upregulated in more mature neurons when they enter the preplate and cortical plate. These patterns suggest that the transition from immature to mature neurons involves sequential changes in the member of fringe family genes expressed. More detailed expression analyses of fringe genes and immunohistochemistry for neuron-specific class III beta-tubulin suggest a mode of neurogenesis which might underlie the histogenesis of the cerebral cortex. A proliferative population situated outside of the VZ is defined as M-fng-positive/BrdU-positive cells, which constitutes about 10-20% of the total S-phase cells in the cerebral wall of embryonic day 10.5-12.5. We found that M-fng is expressed in mitotic figures outside the VZ and some of them react with the antibody against class III beta-tubulin. These observations suggest that a significant number of proliferative cells exist outside the VZ, which supply neurons during early cortical development.

Animals↗

Ferret pyramidal cell dendritogenesis: changes in morphology and ganglioside expression during cortical development.

Pyramidal cell ontogenesis and basilar dendritic differentiation were evaluated concomitantly with ganglioside expression and distribution in ferret cerebral cortex. Layer V neurons began basilar dendritogenesis on postnatal day 1 (P1) with a peak in dendritic arborization occurring at P21. Layer II/III neurons, in contrast, were in early stages of basilar dendritic differentiation at P14, resulting in a complex dendritic arbor at P28. High performance thin-layer chromatography showed numerous changes in ganglioside expression during cortical development, including a decline of GM2 in the mature cortex. The temporal expression and cellular distribution of GM2, GD2, GM1, GD3, and GM3 gangliosides in developing cerebral cortex were determined by immunocytochemistry. GM2 immunoreactivity (IR) was most prominent in layer V neurons between P1 and P21 and in layer II/III neurons between P14 and P28 with staining diminishing to near absent levels in the adult. GM2-IR appeared as punctate structures within the somatodendritic domain and by electron microscopy was shown to be membrane-bound vesicles often in close proximity to the plasmalemma. Expression of GM2, but not of other gangliosides studied, followed two well-documented developmental neurogenic gradients: ventrolateral to dorsomedial and radial (inside-first outside-last). Onset of significant GD2 expression in layer II/III and V pyramidal cells was delayed until P14 and persisted in adult neocortex. GD3 was localized most prominently to glial-like cells, whereas GM1 was primarily localized to white matter. The close temporal and spatial concordance of GM2-IR in cortical pyramidal neurons undergoing dendritogenesis is consistent with its proposed role as a modulator of dendritic differentiation.

Aging↗

Periventricular heterotopia: an X-linked dominant epilepsy locus causing aberrant cerebral cortical development.

Periventricular heterotopia (PH) involves dramatic malformations of the human cerebral cortex. Here we show that PH is closely linked to markers in distal Xq28 (maximal two-point lod score = 4.77 for F8C at theta = 0; maximal multipoint lod score = 5.37), so that affected females are obligatory mosaics for the mutation; that PH is lethal to at least some affected males; that PH malformations consist of well-differentiated cortical neurons filling the adult subependymal zone; and that individuals with PH are at high risk for epilepsy, though they have no other neurological or external stigmata. The PH gene may represent an important epilepsy susceptibility locus in addition to playing a key role in normal cortical development.

Abortion, Habitual↗

Abnormal cortical development; towards elucidation of the LIS1 gene product function (review).

Lissencephaly is a relatively common brain malformation. Lissencephaly type 1 is characterized by the smooth appearance of the cortex and the presence of four abnormally positioned layers instead of the normal six. Lissencephaly is considered to be an abnormality in neuronal migration. The gene mutated in type 1 lissencephaly was cloned by us and designated LIS1. Recently, several genes involved in cortical development have been cloned in the mouse. In human an additional X-linked lissencephaly gene has been identified. We summarize here our current knowledge on the LIS1 gene and its function. It has been identified as a non-catalytic subunit of PAF-acetylhydrolase, a heterotrimeric enzyme which inactivates the platelet-activating factor (PAF). In addition, we have demonstrated that LIS1 interacts with tubulin, and affects the dynamics properties of microtubles. LIS1 contains seven WD repeats and may structurally resemble the beta-subunit of heterotrimeric G proteins. Interestingly, the catalytic subunit of PAF-acetylhydrolase was found to resemble the alpha subunit of heterotrimeric G proteins. We raise the possibility that LIS1 is part of an intracellular signaling pathway involved in neuronal migration.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Telencephalon-specific Rb knockouts reveal enhanced neurogenesis, survival and abnormal cortical development.

Correct cell cycle regulation and terminal mitosis are critical for nervous system development. The retinoblastoma (Rb) protein is a key regulator of these processes, as Rb-/- embryos die by E15.5, exhibiting gross hematopoietic and neurological defects. The extensive apoptosis in Rb-/- embryos has been attributed to aberrant S phase entry resulting in conflicting growth control signals in differentiating cells. To assess the role of Rb in cortical development in the absence of other embryonic defects, we examined mice with telencephalon-specific Rb deletions. Animals carrying a floxed Rb allele were interbred with mice in which cre was knocked into the Foxg1 locus. Unlike germline knockouts, mice specifically deleted for Rb in the developing telencephalon survived until birth. In these mutants, Rb-/- progenitor cells divided ectopically, but were able to survive and differentiate. Mutant brains exhibited enhanced cellularity due to increased proliferation of neuroblasts. These studies demonstrate that: (i) cell cycle deregulation during differentiation does not necessitate apoptosis; (ii) Rb-deficient mutants exhibit enhanced neuroblast proliferation; and (iii) terminal mitosis may not be required to initiate differentiation.

Alleles↗

Functional neuroimaging of malformations of cortical development.

Functional neuroimaging over the past 10 years has led to greater insights into the pathophysiology underlying symptomatic epilepsy. Such imaging has been used to localize cerebral dysfunction, predominantly through disturbances in metabolism or blood flow. Techniques available include single photon emission computed tomography (SPECT), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Although the use of these diagnostic techniques is widely reported for presurgical evaluation, there has been little work with specific reference to malformations of cortical development.

Adolescent↗

Advanced microscopic imaging methods to investigate cortical development and the etiology of mental retardation.

Studies on human patients and animal models of disease have shown that disruptions in prenatal and early postnatal brain development are a root cause of mental retardation. Since proper brain development is achieved by a strict spatiotemporal control of neurogenesis, cell migration, and patterning of synapses, abnormalities in one or more of these events during prenatal development can lead to cognitive dysfunction after birth. Many of underlying causes of mental retardation must therefore be studied in developing brains. To aid in this research, live imaging using laser scanning microscopy (LSM) has recently allowed neuroscientists to delve deeply into the complex three-dimensional environment of the living brain to record dynamic cellular events over time. This review will highlight recent examples of how LSM is being applied to elucidate both normal and abnormal cortical development.

Absorptiometry, Photon↗

Receptor related to tyrosine kinase RYK regulates cell migration during cortical development.

Mammalian RYK is a receptor related to tyrosine kinase without detectable catalytic activity. We have previously reported that rat RYK is dominantly expressed in neural progenitor cells and mature neurons in the developing central nervous system. Mouse RYK has been found to bind to EphB2/B3 receptors, which have diverse functions during development. In this study, we demonstrated that RYK, EphB2, EphB3, ephrinB1, and ephrinB2 are expressed in embryonic brain. In vitro analysis using COS-7 cells revealed binding between rat RYK and EphB3, and that the RYK deletion mutant without extracellular leucine-rich motifs lacked this binding ability. To investigate the function of RYK in vivo, embryonic cortical slice cultures were analyzed after electroporation of expression plasmids for RYK or its deletion mutants. The results showed that overexpression of RYK suppressed cell migration from the ventricular zone to the pial surface, however, overexpression of the RYK deletion mutant without leucine-rich motifs had no effect on cell migration. These results suggest that RYK regulates cell migration during mammalian cortical development through the binding to Eph receptors.

Animals↗

Facial hemangioma and malformation of the cortical development: a broadening of the PHACE spectrum or a new entity?

Facial hemangioma is usually isolated but its association with craniocervical arterial anomalies and structural brain malformations is well known. The acronym PHACE syndrome (posterior fossa malformation, facial hemangiomas, arterial anomalies, cardiac/aortic anomalies, and eye abnormalities) has been used to indicate that disorder in which brain anomalies are mainly represented by the Dandy-Walker malformation. We report on a 10-month-old boy affected by facial hemangioma and a complex cortical dysplasia located in the left frontal region. The lesion was characterized by a deeply infolding pachygyric cortex and a band of gray matter lining the wall of the lateral ventricle. The entire left cerebral hemisphere appeared hypoplastic. No anomalies of the posterior fossa structures or cardiac/aortic malformations were present. An overlapping clinical/pathological pattern was previously reported in another patient with facial hemangioma and cerebrovascular anomalies. These observations seem to indicate that the facial hemangiomas may be associated with disorders of the cortical development.

Abnormalities, Multiple↗

[Functional reorganization of language in a case of cortical development disorder with continuous spike and wave during sleep].

INTRODUCTION: Left cerebral hemisphere dominance for language is a well known fact. However, this typical lateralization may be affected when left hemisphere is damaged at an early age. In this case, neuronal plasticity allows language to be totally or partially transferred to another area within the ipsilateral or contralateral hemisphere. CASE REPORT: 21 year old woman. Congenital right hemiparesis. Focal epilepsy and continuous spike and wave during NREM sleep at 4 years old. Magnetic resonance imaging: extensive malformation of cortical development in the left hemisphere. From 7 years old, seizures were controlled and the continuous spike and wave discharges disappeared. TREATMENT: Valproic acid, 500 mg/day. Neuropsychological assessment showed that basic language functions were well preserved, while there were signs of non-dominant hemisphere dysfunction. These paradoxical results, together with the fact that the patient was left-handed, established the possibility of functional reorganization of language to the right hemisphere. A functional magnetic resonance imaging (fMRI) study for language lateralization demonstrated preferential right hemisphere activation on Broca's and Wernicke's areas. CONCLUSIONS: This case shows the brain's potential for functional reorganization, especially if, according to Kennard's principle, the injury is produced at an early age.

Adult↗

Changes in the distribution of extracellular matrix components accompany early morphogenetic events of mammalian cortical development.

As a step in defining the molecular environment for development of the mammalian cerebral cortex, we have used immunohistochemistry to analyze the distribution and remodeling of three major extracellular matrix (ECM) components, fibronectin, chondroitin sulfate proteoglycan (CSPG), and tenascin, during embryonic and early postnatal stages in the mouse. Fibronectin and CSPG are distributed throughout the proliferative zone that initially comprises the thin wall of the telencephalic vesicle, but their distribution changes as newly generated cells form the preplate just beneath the pia. Immunolabeling for CSPG becomes most prominent in the preplate, and fibronectin becomes restricted to that layer. Just after this change occurs, processes of preplate neurons, visualized with antibodies to neurofilaments, become evident within the matrix-rich preplate zone. The association of fibronectin and CSPG with preplate cells persists as cortical plate neurons divide the preplate; both ECM components are now most prominent in the marginal zone and subplate, the layers above and below the cortical plate that are preplate derived. Within the preplate and its derivatives, immunolabeling of fibronectin is punctate and closely associated with radial glial processes, while labeling of CSPG is more intense and diffuse. Labeling of fibronectin and CSPG declines rapidly as the cortical plate begins to differentiate into cortex; labeling for tenascin first appears at this stage in the most mature layers, the marginal zone and subplate, then gradually becomes widespread throughout all of cortex and subcortical white matter. In early postnatal life, tenascin is eliminated from the hollows of the vibrissal barrels in the somatosensory region; it then declines rapidly throughout cortex. The association of both fibronectin and CSPG with preplate cells and the distribution of fibronectin along radial glia during early cortical development suggest that one or both of these transient cell types might produce specific ECM components or induce their local deposition. The spatial and temporal distribution of fibronectin and CSPG suggests a role in defining a destination for migrating neurons that form the cortical plate and in delineating the pathway for early axonal extension. In contrast, the relatively late appearance of tenascin correlates best with the formation of astrocytes and their processes rather than with the establishment of cortical layers or major axonal pathways. These events are well underway before labeling of tenascin is evident.

Animals↗

Defective cell cycle control underlies abnormal cortical development in the hydrocephalic Texas rat.

There is a significant body of evidence to suggest a physiological role for the CSF in both the developing and adult brain. Our recent studies suggest a critical role for this fluid in the developing brain of the hydrocephalic Texas (H-Tx) rat. A key feature of the foetal-onset hydrocephalus in this rat is obstruction in the flow and/or absorption of fluid that is associated with abnormal development of the cerebral cortex resulting in a reduction in the number of neuronal precursors generated. Cells from the affected cerebral cortex do proliferate in vitro and show dose-dependent responses to growth factor stimulation, suggesting that germinal cells are under inhibitory influences in vivo. We tested the hypothesis that the CSF of the affected brains was responsible for the abnormal development. Cells analysed at the time of extraction from affected brains showed an accumulation of cells in the S-phase of the cell cycle, which was reflected in a concentration of cells containing high levels of DNA in the germinal matrix of histological sections of affected brains. CSF from the lateral ventricle of affected foetal brains not only inhibited in vitro proliferation of normal neuronal progenitors, but it also resulted in an accumulation of cells in the S-phase of the cell cycle mimicking the situation in vivo. Fluid from normal foetal brains did not have this effect. From the work detailed here on the mechanistic basis of the deficient cortical development in the foetal hydrocephalic rat brain, we conclude that the content of the CSF is critical in maintaining germinal matrix function and output and, therefore, that the CSF has a vital role in brain development.

Animals↗

Brain-derived neurotrophic factor-induced potentiation of Ca(2+) oscillations in developing cortical neurons.

Brain-derived neurotrophic factor (BDNF) has been reported to exert an acute potentiation of synaptic activity. Here we examined the action of BDNF on synchronous spontaneous Ca(2+) oscillations in cultured cerebral cortical neurons prepared from postnatal 2-3-day-old rats. The synchronous spontaneous Ca(2+) oscillations began at approximately DIV 5. It was revealed that voltage-dependent Ca(2+) channels and ionotropic glutamate receptors were involved in the synchronous spontaneous oscillatory activity. BDNF potentiated the frequency of these oscillations. The BDNF-potentiated activity reached 207 +/- 20.1% of basal oscillatory activity. NT-3 and NT-4/5 also induced the potentiation. However, nerve growth factor did not. We examined the correlation between BDNF-induced glutamate release and the BDNF-potentiated oscillatory activity. Both up-regulation of phospholipase C-gamma (PLC-gamma) expression and the BDNF-induced glutamate release occurred at approximately DIV 5 when the BDNF-potentiated oscillations appeared. We confirmed that the BDNF-induced glutamate release occurred through a glutamate transporter that was dependent on the PLC-gamma/IP(3)/Ca(2+) pathway. Transporter inhibitors blocked the BDNF-potentiated oscillations, demonstrating that BDNF enhanced the glutamatergic transmissions in the developing cortical network by inducing glutamate release via a glutamate transporter.

Amino Acid Transport System X-AG↗

The Reelin signaling pathway in mouse cortical development.

Most of the cerebral cortex derives from the cortical plate which, in all mammals, is radially organized and develops from inside to outside. Several genes involved in the organization and inside-outside development of the embryonic cortical plate in the mouse form the so-called Reelin signaling pathway. Biochemical and genetic arguments show that the extracellular matrix protein Reelin binds to two lipoprotein receptors (VLDLR and ApoER2), which relay the Reelin signal inside target neurons by docking the tyrosine kinase adapter disabled-1 (Dab1). In addition, biochemical evidence suggests that the integrins alpha 3/beta 1 and protocadherins of the CNR family may also modulate the Reelin signal. The mechanisms by which the presence of Reelin stops migration and instructs the radial organization of cortical plate cells remains unknown.

Animals↗

A new view of early cortical development.

Recently, several genes that regulate the development of the cerebral cortex and are potential pharmacological targets have been cloned. Reelin, an extracellular matrix glycoprotein secreted by Cajal-Retzius cells in the marginal zone, instructs the radial organization of the cortical plate. The response of cortical plate cells to reelin requires the tyrosine kinase adaptor disabled-1 (Dab1). Cyclin-dependent kinase 5 and its activator p35 are necessary for the development of the cortical plate, probably at a later stage than reelin/Dab1. The transcription factor Tbr-1 is essential for differentiation of preplate and Cajal-Retzius cells and for formation of thalamocortical connections, while D1x-1/2 are required for tangential migration. Some neurotrophin systems such as neurotrophin 4, brain-derived neurotrophic factor, and neuregulin and its receptor ErbB are also thought to assist in the regulation of cortical development. In addition, a few genes implicated in human cortical dysplasias have been characterized. LIS1 encodes a protein related to platelet-activating factor acetyl hydrolase that is defective in lissencephaly-1 of the Miller-Dieker type, while the double cortex malformation is related to mutations of a new gene dubbed doublecortn.

Animals↗

Disruption of cortical development as a consequence of repetitive pilocarpine-induced status epilepticus in rats.

PURPOSE: The aim of the present study was to observe possible cortical abnormalities after repetitive pilocarpine-induced status epilepticus (SE) in rats during development. METHODS: Wistar rats received intraperitoneal injection of pilocarpine hydrochloride 2% (380 mg/kg) at P7, P8, and P9. All experimental rats displayed SE after pilocarpine injections. Rats were killed at P10 and P35, and immunocytochemistry procedures were performed on 50-microm vibratome sections, by using antibodies against nonphosphorylated neurofilament (SMI-311), parvalbumin (PV), calbindin (CB), calretinin (CR), and glutamate decarboxylase (GAD-65). Selected sections were used for the TUNEL method and double-labeling experiments, with different mixtures of the same markers. RESULTS: The major findings of the present work were (a) altered intracortical circuitry development; (b) anticipation of PV immunoreactivity in neocortical interneurons; (c) increased GAD-65 immunoreactivity; and (d) reduced neocortical apoptotic process. CONCLUSIONS: From these results, we suggest that previously healthy brain, without genetic abnormalities, might develop an "acquired" disruption of cortical development whose evolution reproduces some characteristics of the childhood epilepsies associated with cognitive impairment.

Animals↗

EEG features of focal malformations of cortical development.

Recent advances in neuroimaging have allowed the detection and characterization of focal malformations of cortical developmental in a significant proportion of patients with epilepsy, many of whom were previously labelled as cryptogenic, allowing a better description of the associated electroencephalogram (EEG) features. Alpha activity is usually preserved, although superficial gyral abnormalities are often associated with overlying localized polymorphic delta activity, and occasionally abnormal fast activity. Most affected patients with epilepsy show interictal spikes. These are often broadly concordant with the structural abnormality but may show a wider anatomic distribution and be multifocal, or occasionally appear only in anatomically distant sites. In many patients the spikes are frequent and sometimes they occur continuously or in long trains. EEG findings are often stable over time, but some patients only show the development of slow wave changes or interictal spikes when followed serially for several years. A small proportion of patients with focal malformations of cortical development have EEG features mimicking idiopathic generalized epilepsy, and occasionally patients exhibit continuous generalized spike and slow wave activity in sleep. Electrocorticography studies confirm the often widespread nature of interictal spiking, but may also show highly epileptogenic patterns recorded directly from dysplastic cortex. The intrinsic epileptogenicity of areas of cortical developmental abnormalities has also been demonstrated by chronic intracranial studies and in vitro recordings of slices obtained from resected human dysplastic cortex. In this regard such developmental abnormalities are fundamentally different from acquired lesions such as tumors/vascular anomalies that usually exert their effects through changes in adjacent cortex.

Adolescent↗