Screening and functional analyses of the molecules that are preferentially expressed in the upper cortical plate of the developing cerebral cortex

2007 ◽  
Vol 58 ◽  
pp. S203
Author(s):  
Kashiko Tachikawa ◽  
Shinji Sasaki ◽  
Takuya Maeda ◽  
Kazunori Nakajima
Keyword(s):  
Cerebral Cortex ◽  
Cortical Plate ◽  
Functional Analyses

Disabled-1 acts downstream of Reelin in a signaling pathway that controls laminar organization in the mammalian brain

Development ◽  
1998 ◽  
Vol 125 (18) ◽  
pp. 3719-3729 ◽  
Author(s):  
D.S. Rice ◽  
M. Sheldon ◽  
G. D'Arcangelo ◽  
K. Nakajima ◽  
D. Goldowitz ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Signaling Pathway ◽  
Developmental Process ◽  
Cortical Plate ◽  
Mammalian Brain ◽  
Granule Neurons ◽  
Adapter Protein ◽  
Cell Position ◽  
Neuronal Precursors ◽  
Retzius Cells

Mutation of either reelin (Reln) or disabled-1 (Dab1) results in widespread abnormalities in laminar structures throughout the brain and ataxia in reeler and scrambler mice. Both exhibit the same neuroanatomical defects, including cerebellar hypoplasia with Purkinje cell ectopia and disruption of neuronal layers in the cerebral cortex and hippocampus. Despite these phenotypic similarities, Reln and Dab1 have distinct molecular properties. Reln is a large extracellular protein secreted by Cajal-Retzius cells in the forebrain and by granule neurons in the cerebellum. In contrast, Dab1 is a cytoplasmic protein which has properties of an adapter protein that functions in phosphorylation-dependent intracellular signal transduction. Here, we show that Dab1 participates in the same developmental process as Reln. In scrambler mice, neuronal precursors are unable to invade the preplate of the cerebral cortex and consequently, they do not align within the cortical plate. During development, cells expressing Dab1 are located next to those secreting Reln at critical stages of formation of the cerebral cortex, cerebellum and hippocampus, before the first abnormalities in cell position become apparent in either reeler or scrambler. In reeler, the major populations of displaced neurons contain elevated levels of Dab1 protein, although they express normal levels of Dab1 mRNA. This suggests that Dab1 accumulates in the absence of a Reln-evoked signal. Taken together, these results indicate that Dab1 functions downstream of Reln in a signaling pathway that controls cell positioning in the developing brain.

Changing patterns of synaptic input to subplate and cortical plate during development of visual cortex

1991 ◽  
Vol 66 (6) ◽  
pp. 2059-2071 ◽  
Author(s):  
E. Friauf ◽  
C. J. Shatz
Keyword(s):  
Cerebral Cortex ◽  
Visual Cortex ◽  
Synaptic Input ◽  
Field Potential ◽  
Short Latency ◽  
Cortical Plate ◽  
Synaptic Activation ◽  
Cortical Layers ◽  
Subplate Neurons ◽  
Monosynaptic Excitation

1. The development of excitatory activation in the visual cortex was studied in fetal and neonatal cats. During fetal and neonatal life, the immature cerebral cortex (the cortical plate) is sandwiched between two synaptic zones: the marginal zone above, and an area just below the cortical plate, the subplate. The subplate is transient and disappears by approximately 2 mo postnatal. Here we have investigated whether the subplate and the cortical plate receive functional synaptic inputs in the fetus, and when the adultlike pattern of excitatory synaptic input to the cortical plate appears during development. 2. Extracellular field potential recording to electrical stimulation of the optic radiation was performed in slices of cerebral cortex maintained in vitro. Laminar profiles of field potentials were converted by the current-source density (CSD) method to identify the spatial and temporal distribution of neuronal excitation within the subplate and the cortical plate. 3. Between embryonic day 47 (E47) and postnatal day 28 (P28; birth, E65), age-related changes occur in the pattern of synaptic activation of neurons in the cortical plate and the subplate. Early in development, at E47, E57, and P0, short-latency (probably monosynaptic) excitation is most obvious in the subplate, and longer latency (presumably polysynaptic) excitation can be seen in the cortical plate. Synaptic excitation in the subplate is no longer apparent at P21 and P28, a time when cell migration is finally complete and the cortical layers have formed. By contrast, excitation in the cortical plate is prominent in postnatal animals, and the temporal and spatial pattern has changed. 4. The adultlike sequence of synaptic activation in the different cortical layers can be seen by P28. It differs from earlier ages in several respects. First, short-latency (probably monosynaptic) excitation can be detected in cortical layer 4. Second, multisynaptic, long-lasting activation is present in layers 2/3 and 5. 5. Our results show that the subplate zone, known from anatomic studies to be a synaptic neurophil during development, receives functional excitatory inputs from axons that course in the developing white matter. Because the only mature neurons present in this zone are the subplate neurons, we conclude that subplate neurons are the principal, if not the exclusive, recipients of this input. The results suggest further that the excitation in the subplate in turn is relayed to neurons of the cortical plate via axon collaterals of subplate neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals PlexinA4-Semaphorin3A mediated crosstalk between main cortical interneuron classes is required for superficial interneurons lamination

2020 ◽  
Author(s):  
Greta Limoni ◽  
Mathieu Niquille ◽  
Sahana Murthy ◽  
Denis Jabaudon ◽  
Alexandre Dayer
Keyword(s):  
Cerebral Cortex ◽  
Serotonin Receptor ◽  
Deep Layer ◽  
Cortical Plate ◽  
Inhibitory Interneurons ◽  
Cell Type ◽  
Cortical Layers ◽  
Cortical Interneuron ◽  
Cell Type Specific ◽  
Genetic Deletion

SummaryIn the mammalian cerebral cortex, the developmental events governing the allocation of different classes of inhibitory interneurons (INs) into distinct cortical layers are poorly understood. Here we report that the guidance receptor PlexinA4 (PLXNA4) is upregulated in serotonin receptor 3a-expressing (HTR3A+) cortical INs (hINs) as they invade the cortical plate and that it regulates their laminar allocation to superficial cortical layers. We find that the PLXNA4 ligand Semaphorin3A (SEMA3A) acts as a chemorepulsive factor on hINs migrating into the nascent cortex and demonstrate that SEMA3A specifically controls their laminar positioning through PLXNA4. We identify that deep layer INs constitute a major source of SEMA3A in the developing cortex and demonstrate that cell-type specific genetic deletion of SEMA3A in these INs specifically affects the laminar allocation of hINs. These data demonstrate that in the neocortex, deep layer INs control the laminar allocation of hINs into superficial layers.

Tangential migration of neurons in the developing cerebral cortex

Development ◽  
1995 ◽  
Vol 121 (7) ◽  
pp. 2165-2176 ◽  
Author(s):  
N.A. O'Rourke ◽  
D.P. Sullivan ◽  
C.E. Kaznowski ◽  
A.A. Jacobs ◽  
S.K. McConnell
Keyword(s):  
Cerebral Cortex ◽  
Neuronal Migration ◽  
Ventricular Zone ◽  
Brain Slices ◽  
Cortical Plate ◽  
Tangential Migration ◽  
Cortical Regions ◽  
Intact Cortex ◽  
Migrating Cells

The mammalian cerebral cortex is divided into functionally distinct areas. Although radial patterns of neuronal migration have been thought to be essential for patterning these areas, direct observation of migrating cells in cortical brain slices has revealed that cells follow both radial and nonradial pathways as they travel from their sites of origin in the ventricular zone out to their destinations in the cortical plate (O'Rourke, N.A., Dailey, M.E., Smith, S.J. and McConnell, S.K. (1992) Science 258, 299–302). These findings suggested that neurons may not be confined to radial migratory pathways in vivo. Here, we have examined the patterns of neuronal migration in the intact cortex. Analysis of the orientations of [3H]thymidine-labeled migrating cells suggests that nonradial migration is equally common in brain slices and the intact cortex and that it increases during neurogenesis. Additionally, cells appear to follow nonradial trajectories at all levels of the developing cerebral wall, suggesting that tangential migration may be more prevalent than previously suspected from the imaging studies. Immunostaining with neuron-specific antibodies revealed that many tangentially migrating cells are young neurons. These results suggest that tangential migration in the intact cortex plays a pivotal role in the tangential dispersion of clonally related cells revealed by retroviral lineage studies (Walsh, C. and Cepko, C. L. (1992) Science 255, 434–440). Finally, we examined possible substrata for nonradial migration in dorsal cortical regions where the majority of glia extend radially. Using confocal and electron microscopy, we found that nonradially oriented cells run perpendicular to glial processes and make glancing contacts with them along their leading processes. Thus, if nonradial cells utilize glia as a migratory substratum they must glide across one glial fiber to another. Examination of the relationships between migratory cells and axons revealed axonal contacts with both radial and nonradial cells. These results suggest that nonradial cells use strategies and substrata for migration that differ from those employed by radial cells.

Querkopf, a MYST family histone acetyltransferase, is required for normal cerebral cortex development

Development ◽  
2000 ◽  
Vol 127 (12) ◽  
pp. 2537-2548 ◽  
Author(s):  
T. Thomas ◽  
A.K. Voss ◽  
K. Chowdhury ◽  
P. Gruss
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Histone Acetyltransferase ◽  
System Development ◽  
Pyramidal Cells ◽  
Postnatal Period ◽  
Nervous System Development ◽  
Cortical Plate ◽  
Central Nervous System Development

In order to find, and mutate, novel genes required for regulation of neurogenesis in the cerebral cortex, we performed a genetic screen in mice. As the result of this screen, we created a new mouse mutant, querkopf. The querkopf mutation is due to an insertion into a MYST family histone acetyltransferase gene. Mice homozygous for the querkopf mutation have craniofacial abnormalities, fail to thrive in the postnatal period and have defects in central nervous system development. The defects in central nervous system development are particularly prominent in the cerebral cortex, which is disproportionally smaller than in wild-type mice. A large reduction in the size of the cortical plate was already apparent during embryogenesis. Homozygous mice show a lack of large pyramidal cells in layer V of the cortex, which is reflected in a reduction in the number of Otx1-positive neurons in this layer during postnatal development. Homozygous mice also show a reduction in the number of GAD67-positive interneurons throughout the cortex. Our results suggest that Querkopf is an essential component of a genetic cascade regulating cell differentiation in the cortex, probably acting in a multiprotein complex regulating chromatin structure during transcription.

scholarly journals Ariadne’s Thread in the Developing Cerebral Cortex: Mechanisms Enabling the Guiding Role of the Radial Glia Basal Process during Neuron Migration

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 3
Author(s):  
Brandon L. Meyerink ◽  
Neeraj K. Tiwari ◽  
Louis-Jan Pilaz
Keyword(s):  
Cerebral Cortex ◽  
Radial Glia ◽  
Cortical Plate ◽  
Neuron Migration ◽  
Basal Process ◽  
Final Destination ◽  
Entire Thickness ◽  
Migratory Path ◽  
Physical Interactions

Radial neuron migration in the developing cerebral cortex is a complex journey, starting in the germinal zones and ending in the cortical plate. In mice, migratory distances can reach several hundreds of microns, or millimeters in humans. Along the migratory path, radially migrating neurons slither through cellularly dense and complex territories before they reach their final destination in the cortical plate. This task is facilitated by radial glia, the neural stem cells of the developing cortex. Indeed, radial glia have a unique bipolar morphology, enabling them to serve as guides for neuronal migration. The key guiding structure of radial glia is the basal process, which traverses the entire thickness of the developing cortex. Neurons recognize the basal process as their guide and maintain physical interactions with this structure until the end of migration. Thus, the radial glia basal process plays a key role during radial migration. In this review, we highlight the pathways enabling neuron-basal process interactions during migration, as well as the known mechanisms regulating the morphology of the radial glia basal process. Throughout, we describe how dysregulation of these interactions and of basal process morphology can have profound effects on cortical development, and therefore lead to neurodevelopmental diseases.

scholarly journals Fetal Rhesus Monkey First Trimester Zika Virus Infection Impacts Cortical Development in the Second and Third Trimesters

2020 ◽  
Author(s):  
Alice F Tarantal ◽  
Dennis J Hartigan-O’Connor ◽  
Elisa Penna ◽  
Anna Kreutz ◽  
Michele L Martinez ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Zika Virus ◽  
Normal Growth ◽  
First Trimester ◽  
Microglial Cells ◽  
Cortical Plate ◽  
Early Gestation ◽  
Neurotropic Viruses ◽  
Vessel Volume ◽  
Near Term

Abstract Zika virus is a teratogen similar to other neurotropic viruses, notably cytomegalovirus and rubella. The goal of these studies was to address the direct impact of Zika virus on fetal development by inoculating early gestation fetal rhesus monkeys using an ultrasound-guided approach (intraperitoneal vs. intraventricular). Growth and development were monitored across gestation, maternal samples collected, and fetal tissues obtained in the second trimester or near term. Although normal growth and anatomical development were observed, significant morphologic changes were noted in the cerebral cortex at 3-weeks post-Zika virus inoculation including massive alterations in the distribution, density, number, and morphology of microglial cells in proliferative regions of the fetal cerebral cortex; an altered distribution of Tbr2+ neural precursor cells; increased diameter and volume of blood vessels in the cortical proliferative zones; and a thinner cortical plate. At 3-months postinoculation, alterations in morphology, distribution, and density of microglial cells were also observed with an increase in blood vessel volume; and a thinner cortical plate. Only transient maternal viremia was observed but sustained maternal immune activation was detected. Overall, these studies suggest persistent changes in cortical structure result from early gestation Zika virus exposure with durable effects on microglial cells.

scholarly journals Brain-synthesized estrogens regulate cortical migration in a sexually divergent manner

2019 ◽  
Author(s):  
Katherine J. Sellers ◽  
Matthew C.S. Denley ◽  
Atsushi Saito ◽  
Atsushi Kamiya ◽  
Deepak P. Srivastava
Keyword(s):  
Cerebral Cortex ◽  
Opposite Effect ◽  
Ventricular Zone ◽  
Cortical Plate ◽  
Local Synthesis ◽  
Male And Female ◽  
Sexual Dimorphisms ◽  
Female Mice ◽  
Males And Females

AbstractEstrogens play an important role in the sexual dimorphisms that occur during brain development, including the neural circuitry that underlies sex-typical and socio-aggressive behaviors. Aromatase, the enzyme responsible for the conversion of androgens to estrogens, is expressed at high levels during early development in both male and female cortices, suggesting a role for brain-synthesized estrogens during corticogenesis. This study investigated how the local synthesis of estrogens affects neurodevelopment of the cerebral cortex, and how this differs in males and females by knockdown expression of the Cyp19a1 gene, which encodes aromatase, between embryonic day 14.5 and postnatal day 0 (P0). The effects of Cyp19a1 knockdown on neural migration was then assessed. Aromatase was expressed in the developing cortex of both sexes, but at significantly higher levels in male than female mice. Under basal conditions, no obvious differences in cortical migration between male and female mice were observed. However, knockdown of Cyp19a1 increased the number GFP-positive cells in the cortical plate, with a concurrent decrease in the subventricular zone/ventricular zone in P0 male mice. The opposite effect was observed in females, with a significantly reduced number of GFP-positive cells migrating to the cortical plate. These findings have important implications for our understanding of the role of fetal steroids for neuronal migration during cerebral cortex development. Moreover, these data indicate that brain-synthesized estrogens regulate radial migration through distinct mechanisms in males and females.

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