Shaping the cerebral cortex by cellular crosstalk

Stoufflet, Julie; Tielens, Sylvia; Nguyen, Laurent

doi:10.1016/j.cell.2023.05.040

Cited by 10 publications

(5 citation statements)

References 146 publications

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“…During neurogenesis, newborn neurons migrate along the radial glial fibers to their appropriate destinations, a process orchestrated both intrinsically and extrinsically. 27,28 DCX has been reported to play a role in neuronal migration through the regulation of microtubule organization and stability in neurons, 6,7 which represents an intrinsic mechanism of neuron migration. The structural integration of radial glial fibers provides some of the extrinsic factors for neuronal migration.…”

Section: Resultsmentioning

confidence: 99%

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DCXknockout ferret reveals a neurogenic mechanism in cortical development

Wang,

Yin,

Wen

et al. 2024

Preprint

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SUMMARYDoublecortin (DCX) is one of the major causal proteins leading to lissencephaly and subcortical band heterotopia in human patients. However, our understanding of this disease, as well as the function of DCX during neurogenesis, remains limited due to the absence of suitable animal models that accurately represent human phenotypes. Here, we conducted a comprehensive examination of the neocortex at different stages inDCXknockout ferrets. We corroborated the neurogenic functions ofDCXin progenitors. Loss of function of DCX led to the over-proliferation of neural progenitors and the truncation of basal processes of radial glial cells, which contributed to the thickening of cortices and the stalling of neurons underneath the cortical plate during neurogenic stages, respectively. We also present the first-ever cell atlas of the lissencephaly disease model, which embraces an almost reversed neuronal lamination distribution in the neocortex compared to the normal controls. Furthermore, we discovered alterations in molecular signatures tied to epilepsy, a condition frequently observed in lissencephaly patients. We also provided compelling evidence that the distribution of GABAergic inhibitory neurons in the cortex is intricately linked to glutamatergic excitatory neurons in a subtype-specific manner. In conclusion, our research offers new insights to expand our understanding of DCX’s functions and enrich our comprehension of lissencephaly’s intricacies.HighlightsDCXferrets phenocopy human lissencephaly and subcortical band heterotopia syndromeDCXis required for NPC proliferation and radial glial basal fiber extensionThe atlas of lissencephalic cortex is illustrated using snRNA-seq and spatial transcriptomeInhibitory neurons couple to excitatory neurons in a cell-type specific manner

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Section: Resultsmentioning

confidence: 99%

Section: Radial Glial Process Defects Contributed To the Aberrant Dis...mentioning

confidence: 99%

DCXknockout ferret reveals a neurogenic mechanism in cortical development

Wang,

Yin,

Wen

et al. 2024

Preprint

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“…The enrichment of chr1q gain associated DEGs for genes involved in cell adhesion and migration suggests that chr1q gain disrupts the developmental migration of neuronal and glial progenitor cells, which is supported clinically by white matter T2-FLAIR hyperintensity with blurring of the gray-white border in the right frontal horn on MRI and the appearance of increased heterotopic neurons in subcortical white matter on neuropathology. Although excitatory neurons and inhibitory neurons are traditionally thought to arise from distinct pools of precursor cells originating from different regions of the developing brain [ 15 ], the presence of chr1q gain in both excitatory and inhibitory neurons (as well as astrocytes) in our patient is in line with the recent finding that a subset of cortical progenitor cells can potentially give rise to both excitatory and inhibitory neurons during human brain development [ 16 ]. The hypothesis that chr1q gain occurred in a cortical progenitor cell during neurodevelopment would also be consistent with in vitro data showing that chr1q gain confers a proliferative advantage in neural stem cells [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Cell type specificity of mosaic chromosome 1q gain resolved by snRNA-seq in a case of epilepsy with hyaline protoplasmic astrocytopathy

Leng,

Cadwell,

Devine

et al. 2023

Preprint

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Introduction: Mosaic gain of chromosome 1q (chr1q) is a recently described driver of malformation of cortical development (MCD) and epilepsy. Hyaline protoplasmic astrocytopathy (HPA) is a rare neuropathological finding seen in cases of epilepsy with MCD. The cell-type specificity of mosaic chr1q gain in the brain and the molecular signatures of HPA are unknown. Methods: We present a child with pharmacoresistant epilepsy who underwent epileptic focus resections at age 3 and 5 years and was found to have mosaic chr1q gain and HPA. We performed single-nucleus RNA-sequencing (snRNA-seq) of brain tissue from the second resection. Results: Remarkably, snRNA-seq showed increased expression of chr1q genes only in subsets of neurons and astrocytes. Differentially expressed genes associated with inferred chr1q gain included AKT3 and genes associated with cell adhesion or migration. A subpopulation of astrocytes demonstrated marked enrichment for synapse-associated transcripts, possibly linked to the astrocytic inclusions observed in HPA. Discussion: snRNA-seq may be used to infer the cell type-specificity of mosaic chromosomal copy number changes and identify associated gene expression alterations, which in the case of chr1q gain may involve aberrations in cell migration. Future studies using spatial profiling could yield further insights on the molecular signatures of HPA.

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“…In living organisms, cellular communication is essential for the cellular decision-making process [1][2][3][4][5][6][7][8][9]. Such communication is established by transmitting the information either from one cell to another by following the inter-cellular signaling-network [9][10][11][12] or by the communication among the cellular components inside a cell through the intra-cellular signaling-pathway [13][14][15][16][17][18]. Cellular information is generally transmitted by the signaling molecules, called ligands, which bind to the receptor proteins on the cell surface [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Elucidating the link between binding statistics and Shannon information in biological cooperative networks

Banerjee,

Das

2024

Preprint

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Cooperative response is ubiquitous and vital for regulatory control and ultra-sensitivity in various cellular biophysical processes. Ligands, acting as signaling molecules, carry information which is transmitted through the elements of the biochemical network during binding processes. In this work, we address a fundamental issue regarding the link between the information content of the various states of the binding network and the observable binding statistics. Two seminal models of cooperativity, viz, the Koshland-Nemethy-Filmer (KNF) network and the Monod-Wyman-Changeux (MWC) network are considered for this purpose which are solved using the chemical master equation approach. Our results establish that the variation of Shannon information associated with the network states has a generic form related to the average binding number. Further, the logarithmic sensitivity of the slope of Shannon information is shown to be related to the Hill slope in terms of the variance of the binding number distributions.

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Shaping the cerebral cortex by cellular crosstalk

Cited by 10 publications

References 146 publications

DCXknockout ferret reveals a neurogenic mechanism in cortical development

DCXknockout ferret reveals a neurogenic mechanism in cortical development

Cell type specificity of mosaic chromosome 1q gain resolved by snRNA-seq in a case of epilepsy with hyaline protoplasmic astrocytopathy

Elucidating the link between binding statistics and Shannon information in biological cooperative networks

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