Cellular migration patterns in the developing mouse cerebral cortex

Development ◽  
1990 ◽  
Vol 110 (3) ◽  
pp. 713-732 ◽  
Author(s):  
C.P. Austin ◽  
C.L. Cepko
Keyword(s):  
Cortical Neurons ◽  
Intermediate Zone ◽  
Cellular Migration ◽  
Three Dimensions ◽  
Cortical Plate ◽  
Cortical Cells ◽  
Migration Patterns ◽  
Embryonic Mouse ◽  
Radial Migration ◽  
Almost All

The migration patterns of embryonic mouse cortical cells were investigated using a replication-incompetent retrovirus vector (BAG). The lateral ventricles of embryonic day 12 mouse embryos were infected with BAG and brains were harvested 2, 3, 4 and 6 days after infection. The location and morphology of all infected cortical cells were recorded from serial sections of entire brains, which were then reconstructed in three dimensions. Examination of the distribution of labelled cells revealed that there were migration patterns characteristic of each medial-lateral domain of the cortex. In the medial and dorsal areas, migration was often radial, although tangential spread increased with survival time, in large part due to ramification of cells in the intermediate zone. In the dorsolateral and lateral areas of the cortex, radial migration was generally not observed. Rather, variable extents of tangential migration occurred, and often resulted in wide separation of cells in the cortical plate. Almost all of the cellular dispersion occurred in the intermediate zone, although a modest degree of dispersion also occurred within the cortical plate itself. Most dispersion occurred in the mediolateral plane, with relatively little dispersion along the anteroposterior axis. Though characteristic migration patterns could be defined, wide variability in the extents of radial migration and tangential separation of cells was seen. The patterns of migration paralleled the distribution of radial glial fibers in all areas, and are most likely a reflection of the role of this network in supporting the migration of cortical neurons. The extent and variability of cellular dispersion supports a lineage-independent mechanism of cortical column ontogenesis.

scholarly journals Dab2IP Regulates Neuronal Positioning, Rap1 Activity and Integrin Signaling in the Developing Cortex

2015 ◽  
Vol 37 (2) ◽  
pp. 131-141 ◽  
Author(s):  
Shuhong Qiao ◽  
Ramin Homayouni
Keyword(s):  
Brain Development ◽  
Cortical Neurons ◽  
Ventricular Zone ◽  
Physiological Role ◽  
Immunohistochemical Analysis ◽  
Superficial Layer ◽  
Tumor Formation ◽  
Intermediate Zone ◽  
Cortical Plate ◽  
Integrin Signaling

Dab2IP (DOC-2/DAB2 interacting protein) is a GTPase-activating protein which is involved in various aspects of brain development in addition to its roles in tumor formation and apoptosis in other systems. In this study, we carefully examined the expression profile of Dab2IP and investigated its physiological role during brain development using a Dab2IP-knockdown (KD) mouse model created by retroviral insertion of a LacZ-encoding gene-trapping cassette. LacZ staining revealed that Dab2IP is expressed in the ventricular zone as well as the cortical plate and the intermediate zone. Immunohistochemical analysis showed that Dab2IP protein is localized in the leading process and proximal cytoplasmic regions of migrating neurons in the intermediate zone. Bromodeoxyuridine birth dating experiments in combination with immunohistochemical analysis using layer-specific markers showed that Dab2IP is important for proper positioning of a subset of layer II-IV neurons in the developing cortex. Notably, neuronal migration was not completely disrupted in the cerebral cortex of Dab2IP-KD mice and disruption of migration was not strictly layer specific. Previously, we found that Dab2IP regulates multipolar transition in cortical neurons. Others have shown that Rap1 regulates the transition from multipolar to bipolar morphology in migrating postmitotic neurons through N-cadherin signaling and somal translocation in the superficial layer of the cortical plate through integrin signaling. Therefore, we examined whether Rap1 and integrin signaling were affected in Dab2IP-KD brains. We found that Dab2IP-KD resulted in higher levels of activated Rap1 and integrin in the developing cortex. Taken together, our results suggest that Dab2IP plays an important role in the migration and positioning of a subpopulation of later-born (layers II-IV) neurons, likely through the regulation of Rap1 and integrin signaling.

scholarly journals Dynein activating adaptor BICD2 controls radial migration of upper-layer cortical neurons in vivo

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Lena Will ◽  
Sybren Portegies ◽  
Jasper van Schelt ◽  
Merel van Luyk ◽  
Dick Jaarsma ◽  
...  
Keyword(s):  
Cortical Neuron ◽  
Cortical Neurons ◽  
Cortical Development ◽  
Adaptor Protein ◽  
Cortical Plate ◽  
Neuron Migration ◽  
Knock Out ◽  
Radial Migration

Abstract For the proper organization of the six-layered mammalian neocortex it is required that neurons migrate radially from their place of birth towards their designated destination. The molecular machinery underlying this neuronal migration is still poorly understood. The dynein-adaptor protein BICD2 is associated with a spectrum of human neurological diseases, including malformations of cortical development. Previous studies have shown that knockdown of BICD2 interferes with interkinetic nuclear migration in radial glial progenitor cells, and that Bicd2-deficient mice display an altered laminar organization of the cerebellum and the neocortex. However, the precise in vivo role of BICD2 in neocortical development remains unclear. By comparing cell-type specific conditional Bicd2 knock-out mice, we found that radial migration in the cortex predominantly depends on BICD2 function in post-mitotic neurons. Neuron-specific Bicd2 cKO mice showed severely impaired radial migration of late-born upper-layer neurons. BICD2 depletion in cortical neurons interfered with proper Golgi organization, and neuronal maturation and survival of cortical plate neurons. Single-neuron labeling revealed a specific role of BICD2 in bipolar locomotion. Rescue experiments with wildtype and disease-related mutant BICD2 constructs revealed that a point-mutation in the RAB6/RANBP2-binding-domain, associated with cortical malformation in patients, fails to restore proper cortical neuron migration. Together, these findings demonstrate a novel, cell-intrinsic role of BICD2 in cortical neuron migration in vivo and provide new insights into BICD2-dependent dynein-mediated functions during cortical development.

GABAC receptors are functionally expressed in the intermediate zone and regulate radial migration in the embryonic mouse neocortex

Neuroscience ◽  
2010 ◽  
Vol 167 (1) ◽  
pp. 124-134 ◽  
Author(s):  
D.G. Denter ◽  
N. Heck ◽  
T. Riedemann ◽  
R. White ◽  
W. Kilb ◽  
...  
Keyword(s):  
Intermediate Zone ◽  
Embryonic Mouse ◽  
Radial Migration ◽  
Gabac Receptors

Effects of cholinergic depletion on neuron activities in the cat visual cortex

1987 ◽  
Vol 58 (4) ◽  
pp. 781-794 ◽  
Author(s):  
H. Sato ◽  
Y. Hata ◽  
K. Hagihara ◽  
T. Tsumoto
Keyword(s):  
Visual Cortex ◽  
Cortical Neurons ◽  
Response Magnitude ◽  
Nucleus Basalis ◽  
Visual Responses ◽  
Cortical Cells ◽  
Contralateral Cortex ◽  
Almost All ◽  
Mean Current ◽  
Cholinergic Projection

1. Unilateral lesions of the nucleus basalis magnocellularis (nBM), a source of cholinergic projection to the cerebral cortex, were produced by injection of kainic acid in the cat. The lesions caused a significant reduction in density of choline acetyltransferase-immunoreactive terminals in the visual cortex ipsilateral to the lesions. 2. In the primary visual cortex ipsilateral to the lesions [acetylcholine (ACh)-depleted cortex], about half of the cells had weak or undetectable visual responses, whereas in the contralateral visual cortex almost all the cells had normal responsivity. The response selectivity, such as orientation and direction selectivities, of cortical cells was not affected by the depletion of ACh. 3. The microionophoretic application of ACh to cells under observation facilitated visual responses in 83% of the cells recorded from the ACh-depleted cortex, whereas it suppressed the responses in only 9%. The application of a muscarinic antagonist, atropine, to cells in the ACh-depleted cortex was ineffective, suggesting no residual ACh activity. 4. The mean current required to induce facilitation in the cortex ipsilateral to the lesion was significantly smaller than that required in the contralateral cortex and the visual cortex of the normal cat, suggesting a supersensitivity of receptors mediating the effect or a reduction in catabolism of exogenous ACh in the ACh-depleted cortex. 5. More than half of the cells that had been unresponsive to visual stimuli became clearly responsive during the ACh application. The response magnitude of cortical cells, as a whole, increased to the same degree as that observed during the ACh application in the normal cat. 6. In addition to the decrease in the average response magnitude, there was a remarkable variability in responses of cells to motion of the slit from sweep to sweep in the ACh-depleted cortex. The application of ACh to cortical cells decreased the variability of responses and consequently made the responses much more consistent. 7. These results suggest that without ACh supplied from the nBM, most of the cortical neurons could not respond briskly and consistently to excitatory inputs and that exogenously applied ACh could reverse such an impairment of cortical neurons through intact or even supersensitive postsynaptic receptors.

scholarly journals A CBCT Based Three-Dimensional Assessment of Mandibular Posterior Region for Evaluating the Possibility of Bypassing the Inferior Alveolar Nerve While Placing Dental Implants

Diagnostics ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 406 ◽  
Author(s):  
Mohammed G. Sghaireen ◽  
Kumar Chandan Srivastava ◽  
Deepti Shrivastava ◽  
Kiran Kumar Ganji ◽  
Santosh R. Patil ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Age Groups ◽  
Inferior Alveolar Nerve ◽  
Three Dimensions ◽  
High Rate ◽  
Cortical Plate ◽  
Computed Tomography Images ◽  
Group I ◽  
Linear Distance ◽  
The Right

A high rate of nerve injury and related consequences are seen during implant placement in the posterior mandibular arch. An approach has been proposed to avoid nerve injury by dodging the inferior alveolar nerve (IAN) while placing an implant. A prospective study with a total of 240 CBCT (cone beam computed tomography) images of patients with three dentate statuses, namely, edentulous (group I), partially edentulous (group II) and dentate (group III) were included in the study. The nerve path tracing was done on CBCT images with On-demand 3D software. The three dimensions, i.e., the linear distance from the outer buccal cortical plate to the inferior alveolar nerve (BCPN), linear distance from the outer lingual cortical plate to the inferior alveolar nerve (LCPN) and linear distance from the midpoint of the alveolar crest to the inferior alveolar nerve (ACN) were assessed. The data were presented and analyzed between variables using one-way ANOVA and independent t-test in SPSS version 21.LCPN of the right 1st premolar region (p < 0.05) was significantly different among the groups with edentulous subjects recorded with the minimum value (6.50 ± 1.20 mm). Females were found to have significantly (p < 0.05) less available bone (6.03 ± 1.46 mm) on the right side of the mandibular jaw compared to males in edentulous group of patients. On comparing age groups for partially edentulous subjects, LCPN of the right 1st premolar region had significantly (p < 0.05) less available bone (6.03 ± 0.38 mm) in subjects with age ≥54 years. The IAN follows a lingual course in the molar region and later flips to the buccal side in the premolar region. The LCPN dimension in the 1st and 2nd premolar region was found to be more than 6 mm irrespective of age, gender and side of the jaw. Thus, it can be considered as a suitable site for placing implants while bypassing the IAN with CBCT assessment remaining as the mainstay in the pre-surgical phase.

scholarly journals Maternal Ethanol Exposure Acutely Elevates Src Family Kinase Activity in the Fetal Cortex

2021 ◽  
Author(s):  
Dandan Wang ◽  
Brian W. Howell ◽  
Eric C. Olson
Keyword(s):  
Tyrosine Phosphorylation ◽  
Cortical Neurons ◽  
Molecular Mechanisms ◽  
Fetal Brain ◽  
Ethanol Exposure ◽  
Src Family Kinase ◽  
Cortical Cells ◽  
Signaling Systems ◽  
Sustained Reduction ◽  
Reelin Signaling

AbstractFetal alcohol syndrome (FAS) is characterized by disrupted fetal brain development and postnatal cognitive impairment. The targets of alcohol are diverse, and it is not clear whether there are common underlying molecular mechanisms producing these disruptions. Prior work established that acute ethanol exposure causes a transient increase in tyrosine phosphorylation of multiple proteins in cultured embryonic cortical cells. In this study, we show that a similar tyrosine phosphorylation transient occurs in the fetal brain after maternal dosing with ethanol. Using phospho-specific antibodies and immunohistochemistry, we mapped regions of highest tyrosine phosphorylation in the fetal cerebral cortex and found that areas of dendritic and axonal growth showed elevated tyrosine phosphorylation 10 min after maternal ethanol exposure. These were also areas of Src expression and Src family kinase (SFK) activation loop phosphorylation (pY416) expression. Importantly, maternal pretreatment with the SFK inhibitor dasatinib completely prevents both the pY416 increase and the tyrosine phosphorylation response. The phosphorylation response was observed in the perisomatic region and neurites of immature migrating and differentiating primary neurons. Importantly, the initial phosphotyrosine transient (~ 30 min) targets both Src and Dab1, two critical elements in Reelin signaling, a pathway required for normal cortical development. This initial phosphorylation response is followed by sustained reduction in Ser3 phosphorylation of n-cofilin, a critical actin severing protein and an identified downstream effector of Reelin signaling. This biochemical disruption is associated with sustained reduction of F-actin content and disrupted Golgi apparatus morphology in developing cortical neurons. The finding outlines a model in which the initial activation of SFKs by ethanol has the potential to disrupt multiple developmentally important signaling systems for several hours after maternal exposure.

scholarly journals BMP signaling and radial migration of cortical neurons

2017 ◽  
Vol 145 ◽  
pp. S115
Author(s):  
Nitin Agnihotri ◽  
Monika Saxena ◽  
Jonaki Sen
Keyword(s):  
Cortical Neurons ◽  
Bmp Signaling ◽  
Radial Migration

scholarly journals Reelin Signals through Phosphatidylinositol 3-Kinase and Akt To Control Cortical Development and through mTor To Regulate Dendritic Growth

2007 ◽  
Vol 27 (20) ◽  
pp. 7113-7124 ◽  
Author(s):  
Yves Jossin ◽  
André M. Goffinet
Keyword(s):  
Cortical Neurons ◽  
Hippocampal Neurons ◽  
Matrix Protein ◽  
Glycogen Synthase ◽  
Extracellular Matrix Protein ◽  
Cortical Plate ◽  
Target Cells ◽  
Neuronal Cultures ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

ABSTRACT Reelin is an extracellular matrix protein with various functions during development and in the mature brain. It activates different signaling cascades in target cells, one of which is the phosphatidylinositol 3-kinase (PI3K) pathway, which we investigated further using pathway inhibitors and in vitro brain slice and neuronal cultures. We show that the mTor (mammalian target of rapamycin)-S6K1 (S6 kinase 1) pathway is activated by Reelin and that this depends on Dab1 (Disabled-1) phosphorylation and activation of PI3K and Akt (protein kinase B). PI3K and Akt are required for the effects of Reelin on the organization of the cortical plate, but their downstream partners mTor and glycogen synthase kinase 3β (GSK3β) are not. On the other hand, mTor, but not GSK3β, mediates the effects of Reelin on the growth and branching of dendrites of hippocampal neurons. In addition, PI3K fosters radial migration of cortical neurons through the intermediate zone, an effect that is independent of Reelin and Akt.

Measurement of cortical plate volume based on CBCT of frontal teeth in studies with retrusion and normality

2021 ◽  
pp. 17-21
Author(s):  
N. G. Meskhiya ◽  
I. S. Kopetskiy ◽  
I. A. Nikolskaya ◽  
D. A. Eremin ◽  
O. N. Kovaleva
Keyword(s):  
Orthodontic Treatment ◽  
Soft Tissues ◽  
Three Dimensions ◽  
Cone Beam ◽  
Cortical Plate ◽  
Imaging Method ◽  
New Approach ◽  
Accuracy Of Measurements ◽  
Bone Structures

Cone Beam Computed Tomography (CBCT) is the preferred imaging method for a comprehensive orthodontic examination. Thanks to the development of this technique, clinicians today can make most accurate measurements without fear of errors associated with projection distortion or localization of landmarks on radiographs. The quality of CBCT images gives to orthodontists the ability to analyze bone structures, teeth (even impacted teeth), and soft tissue in three dimensions. The accuracy of measurements of hard and soft tissues from CBCT images determines the accuracy of diagnosis and treatment planning. A fundamentally new approach has been proposed, which makes it possible to thoroughly study the bone tissue surrounding the tooth at the stages of planning orthodontic treatment. Аnalysis of radiation studies of patients with dentoalveolar anomalies was carried out to select the optimal treatment tactics and to control its effectiveness.

scholarly journals Nucleofection and Primary Culture of Embryonic Mouse Hippocampal and Cortical Neurons

10.3791/2373 ◽  
2011 ◽  
Author(s):  
Christopher Viesselmann ◽  
Jason Ballweg ◽  
Derek Lumbard ◽  
Erik W. Dent
Keyword(s):  
Primary Culture ◽  
Cortical Neurons ◽  
Embryonic Mouse
Sign in / Sign up

Export Citation Format

Share Document