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.

A role for subplate neurons in the patterning of connections from thalamus to neocortex

Development ◽  
1993 ◽  
Vol 117 (3) ◽  
pp. 1031-1047 ◽  
Author(s):  
A. Ghosh ◽  
C.J. Shatz
Keyword(s):  
Auditory Cortex ◽  
Target Selection ◽  
Cortical Plate ◽  
Projection Neurons ◽  
Morphological Development ◽  
Target Area ◽  
Thalamic Nuclei ◽  
Waiting Period ◽  
Subplate Neurons ◽  
Cortical Regions

During cerebral cortical development, ingrowing axons from different thalamic nuclei select and invade their cortical targets. The selection of an appropriate target is first evident even before thalamic axons grow into the cortical plate: initially axons accumulate and wait below their cortical target area in a zone called the subplate. This zone also contains the first postmitotic neurons of the cerebral cortex, the subplate neurons. Here we have investigated whether subplate neurons are involved in the process of target selection by thalamic axons by ablating them from specific cortical regions at the onset of the waiting period and examining the subsequent thalamocortical axon projection patterns. Subplate neurons were ablated at the onset of the waiting period by intracortical injections of kainic acid. The effect of the ablation on the thalamocortical projection from visual thalamus was examined by DiI-labeling of the LGN days to weeks following the lesion. At two to four weeks post-lesion, times when LGN axons would have normally invaded the cortical plate, the axons remained below the cortical plate and grew past their appropriate cortical target in an anomalous pathway. Moreover, examination of LGN axons at one week post-lesion, a time when they would normally be waiting and branching within the visual subplate, indicated that the axons had already grown past their correct destination. These observations suggest that visual subplate neurons are involved in the process by which LGN axons select and subsequently grow into visual cortex. In contrast, subplate neurons do not appear to play a major role in the initial morphological development of the LGN itself. Subplate ablations did not alter dendritic growth or shapes of LGN projection neurons during the period under study, nor did it prevent the segregation of retinal ganglion cell axons into eye-specific layers. However, the overall size of the LGN was reduced, suggesting that there may be increased cell death of LGN neurons in the absence of subplate neurons. To examine whether subplate neurons beneath other neocortical areas play a similar role in the formation of thalamocortical connections, subplate neurons were deleted beneath auditory cortex at the onset of the waiting period for auditory thalamic axons. Subsequent DiI labeling revealed that in these animals the majority of MGN axons had grown past auditory cortex instead of innervating it. Taken together these observations underscore a general requirement for subplate neurons throughout neocortex in the process of cortical target selection and ingrowth by thalamic axons.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Single Cell Transcriptomic Analysis of Spinal Dmrt3 Neurons in Zebrafish and Mouse Identifies Distinct Subtypes and Reveal Novel Subpopulations Within the dI6 Domain

2021 ◽  
Vol 15 ◽  
Author(s):  
Ana Belén Iglesias González ◽  
Jon E. T. Jakobsson ◽  
Jennifer Vieillard ◽  
Malin C. Lagerström ◽  
Klas Kullander ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Axon Guidance ◽  
Single Cell ◽  
Cellular Activity ◽  
Electrophysiological Properties ◽  
Related Transcription Factor ◽  
Unique Markers ◽  
Molecular Code

The spinal locomotor network is frequently used for studies into how neuronal circuits are formed and how cellular activity shape behavioral patterns. A population of dI6 interneurons, marked by the Doublesex and mab-3 related transcription factor 3 (Dmrt3), has been shown to participate in the coordination of locomotion and gaits in horses, mice and zebrafish. Analyses of Dmrt3 neurons based on morphology, functionality and the expression of transcription factors have identified different subtypes. Here we analyzed the transcriptomes of individual cells belonging to the Dmrt3 lineage from zebrafish and mice to unravel the molecular code that underlies their subfunctionalization. Indeed, clustering of Dmrt3 neurons based on their gene expression verified known subtypes and revealed novel populations expressing unique markers. Differences in birth order, differential expression of axon guidance genes, neurotransmitters, and their receptors, as well as genes affecting electrophysiological properties, were identified as factors likely underlying diversity. In addition, the comparison between fish and mice populations offers insights into the evolutionary driven subspecialization concomitant with the emergence of limbed locomotion.

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 The Nuclear Orphan Receptor COUP-TFI Is Required for Differentiation of Subplate Neurons and Guidance of Thalamocortical Axons

Neuron ◽  
1999 ◽  
Vol 24 (4) ◽  
pp. 847-859 ◽  
Author(s):  
Cheng Zhou ◽  
Yuhong Qiu ◽  
Fred A Pereira ◽  
Michael C Crair ◽  
Sophia Y Tsai ◽  
...  
Keyword(s):  
Orphan Receptor ◽  
Thalamocortical Axons ◽  
Subplate Neurons ◽  
Nuclear Orphan Receptor

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 Lhx2 regulates the timing of β-catenin-dependent cortical neurogenesis

2015 ◽  
Vol 112 (39) ◽  
pp. 12199-12204 ◽  
Author(s):  
Lea Chia-Ling Hsu ◽  
Sean Nam ◽  
Yi Cui ◽  
Ching-Pu Chang ◽  
Chia-Fang Wang ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Transcription Factor ◽  
Radial Glia ◽  
Major Effect ◽  
Cortical Surface ◽  
Temporal Shift ◽  
Homeodomain Transcription Factor ◽  
Cortical Neurogenesis ◽  
Underlying Mechanisms ◽  
Cortical Progenitor

The timing of cortical neurogenesis has a major effect on the size and organization of the mature cortex. The deletion of the LIM-homeodomain transcription factor Lhx2 in cortical progenitors by Nestin-cre leads to a dramatically smaller cortex. Here we report that Lhx2 regulates the cortex size by maintaining the cortical progenitor proliferation and delaying the initiation of neurogenesis. The loss of Lhx2 in cortical progenitors results in precocious radial glia differentiation and a temporal shift of cortical neurogenesis. We further investigated the underlying mechanisms at play and demonstrated that in the absence of Lhx2, the Wnt/β-catenin pathway failed to maintain progenitor proliferation. We developed and applied a mathematical model that reveals how precocious neurogenesis affected cortical surface and thickness. Thus, we concluded that Lhx2 is required for β-catenin function in maintaining cortical progenitor proliferation and controls the timing of cortical neurogenesis.

scholarly journals Adult Upper Cortical Layer Specific Transcription Factor CUX2 Is Expressed in Transient Subplate and Marginal Zone Neurons of the Developing Human Brain

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 415
Author(s):  
Terezija Miškić ◽  
Ivica Kostović ◽  
Mladen-Roko Rašin ◽  
Željka Krsnik
Keyword(s):  
Transcription Factor ◽  
Human Brain ◽  
Cortical Neurons ◽  
Marginal Zone ◽  
Synapse Formation ◽  
Cortical Layer ◽  
Cortical Plate ◽  
Projection Neurons ◽  
Cortical Layers ◽  
Spine Development

Cut-Like Homeobox 2 (Cux2) is a transcription factor involved in dendrite and spine development, and synapse formation of projection neurons placed in mouse upper neocortical layers. Therefore, Cux2 is often used as an upper layer marker in the mouse brain. However, expression of its orthologue CUX2 remains unexplored in the human fetal neocortex. Here, we show that CUX2 protein is expressed in transient compartments of developing neocortical anlage during the main fetal phases of neocortical laminar development in human brain. During the early fetal phase when neurons of the upper cortical layers are still radially migrating to reach their final place in the cortical anlage, CUX2 was expressed in the marginal zone (MZ), deep cortical plate, and pre-subplate. During midgestation, CUX2 was still expressed in the migrating upper cortical neurons as well as in the subplate (SP) and MZ neurons. At the term age, CUX2 was expressed in the gyral white matter along with its expected expression in the upper layer neurons. In sum, CUX2 was expressed in migratory neurons of prospective superficial layers and in the diverse subpopulation of transient postmigratory SP and MZ neurons. Therefore, our findings indicate that CUX2 is a novel marker of distinct transient, but critical histogenetic events during corticogenesis. Given the Cux2 functions reported in animal models, our data further suggest that the expression of CUX2 in postmigratory SP and MZ neurons is associated with their unique dendritic and synaptogenesis characteristics.

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 Fundamentals of the Development of Connectivity in the Human Fetal Brain in Late Gestation: From 24 Weeks Gestational Age to Term

2021 ◽  
Vol 80 (5) ◽  
pp. 393-414 ◽  
Author(s):  
Ivica Kostović ◽  
Milan Radoš ◽  
Mirna Kostović-Srzentić ◽  
Željka Krsnik
Keyword(s):  
Large Scale ◽  
Fetal Brain ◽  
Late Gestation ◽  
Cortical Plate ◽  
Future Research ◽  
Thalamocortical Axons ◽  
Extremely Preterm ◽  
Growth Guidance ◽  
Long Term Follow Up ◽  
Histological Data

Abstract During the second half of gestation, the human cerebrum undergoes pivotal histogenetic events that underlie functional connectivity. These include the growth, guidance, selection of axonal pathways, and their first engagement in neuronal networks. Here, we characterize the spatiotemporal patterns of cerebral connectivity in extremely preterm (EPT), very preterm (VPT), preterm and term babies, focusing on magnetic resonance imaging (MRI) and histological data. In the EPT and VPT babies, thalamocortical axons enter into the cortical plate creating the electrical synapses. Additionally, the subplate zone gradually resolves in the preterm and term brain in conjunction with the growth of associative pathways leading to the activation of large-scale neural networks. We demonstrate that specific classes of axonal pathways within cerebral compartments are selectively vulnerable to temporally nested pathogenic factors. In particular, the radial distribution of axonal lesions, that is, radial vulnerability, is a robust predictor of clinical outcome. Furthermore, the subplate tangential nexus that we can visualize using MRI could be an additional marker as pivotal in the development of cortical connectivity. We suggest to direct future research toward the identification of sensitive markers of earlier lesions, the elucidation of genetic mechanisms underlying pathogenesis, and better long-term follow-up using structural and functional MRI.

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.

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