Absence of Cajal-Retzius cells and subplate neurons associated with defects of tangential cell migration from ganglionic eminence in Emx1/2 double mutant cerebral cortex

Development ◽  
2002 ◽  
Vol 129 (14) ◽  
pp. 3479-3492 ◽  
Author(s):  
Koji Shinozaki ◽  
Toshihiko Miyagi ◽  
Michio Yoshida ◽  
Takaki Miyata ◽  
Masaharu Ogawa ◽  
...  
Keyword(s):  
Double Mutant ◽  
Cell Number ◽  
Cortical Plate ◽  
Ganglionic Eminence ◽  
Tetraploid Cell ◽  
Radial Glial Cells ◽  
Gap Gene ◽  
Germinal Zone ◽  
Subplate Neurons ◽  
Retzius Cells

Emx1 and Emx2, mouse orthologs of the Drosophila head gap gene, ems, are expressed during corticogenesis. Emx2 null mutants exhibit mild defects in cortical lamination. Segregation of differentiating neurons from proliferative cells is normal for the most part, however, reelin-positive Cajal-Retzius cells are lost by the late embryonic period. Additionally, late-born cortical plate neurons display abnormal position. These types of lamination defects are subtle in the Emx1 mutant cortex. In the present study we show that Emx1 and Emx2 double mutant neocortex is much more severely affected. Thickness of the cerebral wall was diminished with the decrease in cell number. Bromodeoxyuridine uptake in the germinal zone was nearly normal; moreover, no apparent increase in cell death or tetraploid cell number was observed. However, tangential migration of cells from the ganglionic eminence into the neocortex was greatly inhibited. The wild-type ganglionic eminence cells transplanted into Emx1/2-double mutant telencephalon did not move to the cortex. MAP2-positive neuronal bodies and RC2-positive radial glial cells emerged normally, but the laminar structure subsequently formed was completely abnormal. Furthermore, both corticofugal and corticopetal fibers were predominantly absent in the cortex. Most importantly, neither Cajal-Retzius cells nor subplate neurons were found throughout E11.5-E18.5. Thus, this investigation suggests that laminar organization in the cortex or the production of Cajal-Retzius cells and subplate neurons is interrelated to the tangential movement of cells from the ganglionic eminence under the control of Emx1 and Emx2.

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 Unbiased Quantification of Subplate Neuron Loss following Neonatal Hypoxia-Ischemia in a Rat Model

2017 ◽  
Vol 39 (1-4) ◽  
pp. 171-181 ◽  
Author(s):  
Alexandra Mikhailova ◽  
Naveena Sunkara ◽  
Patrick S. McQuillen
Keyword(s):  
Brain Injury ◽  
Lower Layer ◽  
Cell Number ◽  
Cortical Layer ◽  
Rodent Model ◽  
Cortical Layers ◽  
Cortical Injury ◽  
Neonatal Hypoxia ◽  
Subplate Neurons ◽  
Hypoxia Ischemia

Background: Cellular targets of neonatal hypoxia-ischemia (HI) include both oligodendrocyte and neuronal lineages with differences in the patterns of vulnerable cells depending upon the developmental stage at which the injury occurs. Injury to the developing white matter is a characteristic feature of human preterm brain injury. Data are accumulating, however, for neuronal injury in the developing cerebral cortex. In the most widely used rodent model of preterm HI brain injury, conflicting data have been reported regarding the sensitivity of subplate neurons to early neonatal HI, with some reports of selective vulnerability and others that find no increased loss of subplate neurons in comparison with other cortical layers. Methods used to identify subplate neurons and quantify their numbers vary across studies. Objective: To use recently developed cortical layer-specific markers quantified with definitive stereologic methods to determine the magnitude and specificity of subplate neuron cell loss following neonatal HI in a rodent model. Methods: Postnatal day 2 (P2) rats underwent right common carotid artery coagulation followed by 2-3 h of hypoxia (5.6% oxygen). Categorically moderately injured brains were stained with subplate and cortical layer III-V markers (Complexin3 and Foxp1, respectively) at P8 and P21 (Foxp1 only). An Optical Fractionator was used to quantify subplate and middle/lower cortical neuronal numbers and these were compared across groups (naive control, hypoxia hemisphere, and HI hemisphere). Results: Following HI at P2 in rats, the total Complexin3-expressing subplate neuron number decreases significantly in the HI hemisphere compared with naive controls or hypoxia alone (HI vs. control 26,747 ± 7,952 vs. 35,468 ± 8,029, p = 0.04; HI vs. hypoxia, 26,747 ± 7,952 vs. 40,439 ± 7,363, p = 0.003). In contrast, the total Foxp1-expressing layer III-V cell number did not differ across the 3 conditions at P8 (HI vs. control 1,195,085 ± 436,609 vs. 1,234,640 ± 178,540, p = 0.19; HI vs. hypoxia, 1,195,085 ± 436,609 vs. 1,289,195 ± 468,941, p = 0.35) and at P21 (HI vs. control 1,265,190 ± 48,089 vs. 1,195,632 ± 26,912, p = 0.19; HI vs. hypoxia, 1,265,190 ± 48,089 vs. 1,309,563 ± 41,669, p = 0.49). Conclusions: There is significant biological variability inherent in both the subplate neuron cell number and the pattern and severity of cortical injury following HI at P2 in rats. Despite this variability, the subplate neuron cell number is lower following P2 HI in animals with mild or moderate cortical injury, whereas the middle-to-lower-layer cortical neuronal number is unchanged. In more severe cases, neurons are lost from the lower cortical layers, suggesting a relative vulnerability of subplate neurons.

scholarly journals Functional Nicotinic Acetylcholine Receptors on Subplate Neurons in Neonatal Rat Somatosensory Cortex

2004 ◽  
Vol 92 (1) ◽  
pp. 189-198 ◽  
Author(s):  
Ileana L. Hanganu ◽  
Heiko J. Luhmann
Keyword(s):  
Somatosensory Cortex ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Neonatal Rat ◽  
Cholinergic Innervation ◽  
Cortical Plate ◽  
Nicotinic Acetylcholine ◽  
Synaptic Circuits ◽  
Subplate Neurons ◽  
Rat Somatosensory Cortex

The establishment of cortical synaptic circuits during early development requires the presence of subplate neurons (SPn's), a heterogeneous population of neurons capable to integrate and process synaptic information from the thalamus, cortical plate, and neighboring SPn's. An accumulation of cholinergic afferents and nicotinic acetylcholine receptors (nAChRs) has been documentated in the subplate around birth. To assess the developmental role of the cholinergic innervation onto SPn's, we used whole cell patch-clamp recordings of visually identified and biocytin-labeled SPn's in neonatal rat somatosensory cortex. Functional nAChRs were present in 92% of the investigated SPn's. Activation of postsynaptic nAChRs by local application of agonists elicited a brief membrane depolarization associated with a barrage of action potentials and large inward currents reversing around 0 mV. According to our pharmacological data, excitation of SPn's is mediated by α4β2 receptors. In contrast, functional α7 nAChRs could not be identified on SPn's. Activation of nAChRs affected neither the spontaneous synaptic activity of SPn's nor the synaptic connections between thalamus and SPn's and within subplate. Nicotine, at concentrations reaching the developing brain by maternal smoking, induced a severe desensitization of nAChRs and an increase in the baseline noise. These results indicate that nAChR-mediated excitation of SPn's may stabilize the developing synaptic circuits and suggest the involvement of nAChRs located on SPn's in the fetal tobacco syndrome.

scholarly journals Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity

2020 ◽  
Author(s):  
Daniel Z. Doyle ◽  
Mandy M. Lam ◽  
Adel Qalieh ◽  
Yaman Qalieh ◽  
Alice Sorel ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Axon Guidance ◽  
Neural Circuits ◽  
Cortical Plate ◽  
Chromatin Remodeler ◽  
Cortical Connectivity ◽  
Molecular Identity ◽  
Subplate Neurons ◽  
Cell Type Specific ◽  
And Function

AbstractSubplate neurons indispensably orchestrate the developmental assembly of cortical neural circuits. Here, by cell type-specific dissection of Arid1a function, we uncover an unexpectedly selective role for this ubiquitous chromatin remodeler in subplate neuron molecular identity and circuit wiring function. We find that pan-cortical deletion of Arid1a, but not sparse deletion, leads to mistargeting of callosal and thalamocortical connectivities reminiscent of subplate ablation. These miswiring phenotypes are concomitant with disrupted subplate neuron organization, morphogenesis, axons, and extracellular matrix. Mechanistically, Arid1a is required to establish the transcriptional identity of subplate neurons. Remarkably, cortical plate deletion of Arid1a, which spares subplate neurons, restores subplate axons and extracellular matrix, and is sufficient to extensively correct callosal and thalamocortical axon misrouting, revealing an axon guidance function of Arid1a centered on the subplate. Thus, Arid1a regulates the molecular identity and function of subplate neurons, and thereby non-cell autonomously mediates the formation of cortical connectivity during development.

scholarly journals An early cortical progenitor-specific mechanism regulates thalamocortical innervation

2020 ◽  
Author(s):  
Suranjana Pal ◽  
Deepanjali Dwivedi ◽  
Tuli Pramanik ◽  
Geeta Godbole ◽  
Takuji Iwasato ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cortical Plate ◽  
Specific Mechanism ◽  
Sensory Afferents ◽  
Waiting Period ◽  
Electrophysiological Properties ◽  
Thalamocortical Axons ◽  
Subplate Neurons ◽  
Cortical Progenitor

AbstractThe cortical subplate is critical in regulating the entry of thalamocortical sensory afferents into the cortex. These afferents reach the subplate at embryonic day (E)15.5 in the mouse, but “wait” for several days, entering the cortical plate postnatally. We report that when transcription factor Lhx2 is lost in E11.5 cortical progenitors, which give rise to subplate neurons, thalamocortical afferents display premature, exuberant innervation of the E15.5 cortex. Embryonic mutant subplate neurons are correctly positioned below the cortical plate, but they display an altered transcriptome and immature electrophysiological properties during the waiting period. The sensory thalamus in these cortex-specific Lhx2 mutants displays atrophy, eventually leading to severe deficits in thalamocortical innervation. Strikingly, these phenotypes do not manifest if Lhx2 is lost in postmitotic subplate neurons. These results demonstrate a mechanism operating in subplate progenitors that has profound consequences on the growth of thalamocortical axons into the cortex.

scholarly journals Chromatin remodeler Arid1a regulates subplate neuron identity and wiring of cortical connectivity

2021 ◽  
Vol 118 (21) ◽  
pp. e2100686118
Author(s):  
Daniel Z. Doyle ◽  
Mandy M. Lam ◽  
Adel Qalieh ◽  
Yaman Qalieh ◽  
Alice Sorel ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Corpus Callosum ◽  
Neural Circuit ◽  
Cortical Plate ◽  
Loss Of Function ◽  
Chromatin Remodeler ◽  
Agenesis Of Corpus Callosum ◽  
Axon Targeting ◽  
Subplate Neurons ◽  
Multiple Characteristics

Loss-of-function mutations in chromatin remodeler gene ARID1A are a cause of Coffin-Siris syndrome, a developmental disorder characterized by dysgenesis of corpus callosum. Here, we characterize Arid1a function during cortical development and find unexpectedly selective roles for Arid1a in subplate neurons (SPNs). SPNs, strategically positioned at the interface of cortical gray and white matter, orchestrate multiple developmental processes indispensable for neural circuit wiring. We find that pancortical deletion of Arid1a leads to extensive mistargeting of intracortical axons and agenesis of corpus callosum. Sparse Arid1a deletion, however, does not autonomously misroute callosal axons, implicating noncell-autonomous Arid1a functions in axon guidance. Supporting this possibility, the ascending axons of thalamocortical neurons, which are not autonomously affected by cortical Arid1a deletion, are also disrupted in their pathfinding into cortex and innervation of whisker barrels. Coincident with these miswiring phenotypes, which are reminiscent of subplate ablation, we unbiasedly find a selective loss of SPN gene expression following Arid1a deletion. In addition, multiple characteristics of SPNs crucial to their wiring functions, including subplate organization, subplate axon-thalamocortical axon cofasciculation (“handshake”), and extracellular matrix, are severely disrupted. To empirically test Arid1a sufficiency in subplate, we generate a cortical plate deletion of Arid1a that spares SPNs. In this model, subplate Arid1a expression is sufficient for subplate organization, subplate axon-thalamocortical axon cofasciculation, and subplate extracellular matrix. Consistent with these wiring functions, subplate Arid1a sufficiently enables normal callosum formation, thalamocortical axon targeting, and whisker barrel development. Thus, Arid1a is a multifunctional regulator of subplate-dependent guidance mechanisms essential to cortical circuit wiring.

scholarly journals TOTAL CELL NUMBER IN FETAL BRAIN

2011 ◽  
Vol 19 (1) ◽  
pp. 35 ◽  
Author(s):  
Grethe Badsberg Samuelsen ◽  
Nenad Bogdanović ◽  
Henning Laursen ◽  
Niels Graem ◽  
Jørgen Falck Larsen ◽  
...  
Keyword(s):  
Birth Weight ◽  
Cell Population ◽  
Fetal Brain ◽  
Fold Increase ◽  
Cell Number ◽  
Total Cell ◽  
Cortical Plate ◽  
Total Cell Number ◽  
Normal Birth ◽  
Total Cell Population

In this study the material comprises brains from three aborted fetuses and two fullterm infants who died at birth.The gestational ages ranged from the 22nd week to term. All cases were without malformations, known chromosomal abnormality, hydrops, and systemic infections, and all had normal birth weights with fetal growth indices (observed birth weight/expected mean birth weight) between 0.9 - 1.05. The preliminary results show a five fold increase in the total cell population in the marginal zone/cortical plate, MZ/CP (future neocortex), from week 22 until term. In the transient subplate zone, SP, the total cell number was more than doubled from week 22 to week 30-35, and then decreased towards term. In the intermediate zone, IZ (future white matter), the total cell population was doubled from week 22 until term. The total cell number in the entricular/subventricular zone, VZ/SZ (germinal matrix), was reduced by a factor of five from week 22 until term. A histological differentiation between neurons and glial cells was not possible. The optical fractionator was used to estimate the total cell population in four characteristic developmental zones in the human fetal brain. Fetal brain tissue undergoes considerable and rather unpredictable shrinkage during fixation. However, using the fractionator principle it is possible to eliminate this problem, provided that the structure of interest (one brain hemisphere) is fully intact.

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