scholarly journals Zbtb20 Defines a Hippocampal Neuronal Identity Through Direct Repression of Genes That Control Projection Neuron Development in the Isocortex

2013 ◽  
Vol 24 (5) ◽  
pp. 1216-1229 ◽  
Author(s):  
Jakob V. Nielsen ◽  
Mads Thomassen ◽  
Kjeld Møllgård ◽  
Jens Noraberg ◽  
Niels A. Jensen
Keyword(s):  
Projection Neuron ◽  
Neuron Development ◽  
Neuronal Identity

scholarly journals Re-establishment of the epigenetic state and rescue of kinome deregulation in Ts65Dn mice upon treatment with green tea extract and environmental enrichment

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
I. De Toma ◽  
M. Ortega ◽  
S. Catuara-Solarz ◽  
C. Sierra ◽  
E. Sabidó ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Green Tea ◽  
Environmental Enrichment ◽  
Projection Neuron ◽  
Synaptic Proteins ◽  
Chromosome 21 ◽  
Neuron Development ◽  
Epigenetic State ◽  
Neuronal Projection ◽  
Tea Extract

Abstract Down syndrome (DS) is the main genetic cause of intellectual disability due to triplication of human chromosome 21 (HSA21). Although there is no treatment for intellectual disability, environmental enrichment (EE) and the administration of green tea extracts containing epigallocatechin-3-gallate (EGCG) improve cognition in mouse models and individuals with DS. Using proteome, and phosphoproteome analysis in the hippocampi of a DS mouse model (Ts65Dn), we investigated the possible mechanisms underlying the effects of green tea extracts, EE and their combination. Our results revealed disturbances in cognitive-related (synaptic proteins, neuronal projection, neuron development, microtubule), GTPase/kinase activity and chromatin proteins. Green tea extracts, EE, and their combination restored more than 70% of the phosphoprotein deregulation in Ts65Dn, and induced possible compensatory effects. Our downstream analyses indicate that re-establishment of a proper epigenetic state and rescue of the kinome deregulation may contribute to the cognitive rescue induced by green tea extracts.

scholarly journals Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons

2015 ◽  
Vol 112 (44) ◽  
pp. 13693-13698 ◽  
Author(s):  
Adán de Salas-Quiroga ◽  
Javier Díaz-Alonso ◽  
Daniel García-Rincón ◽  
Floortje Remmers ◽  
David Vega ◽  
...  
Keyword(s):  
Prenatal Exposure ◽  
Cortical Neurons ◽  
Time Window ◽  
Projection Neuron ◽  
Fine Motor ◽  
Adult Offspring ◽  
Neuron Development ◽  
Cortical Projection ◽  
Genetic Ablation ◽  
The Impact

The CB1 cannabinoid receptor, the main target of Δ9-tetrahydrocannabinol (THC), the most prominent psychoactive compound of marijuana, plays a crucial regulatory role in brain development as evidenced by the neurodevelopmental consequences of its manipulation in animal models. Likewise, recreational cannabis use during pregnancy affects brain structure and function of the progeny. However, the precise neurobiological substrates underlying the consequences of prenatal THC exposure remain unknown. As CB1 signaling is known to modulate long-range corticofugal connectivity, we analyzed the impact of THC exposure on cortical projection neuron development. THC administration to pregnant mice in a restricted time window interfered with subcerebral projection neuron generation, thereby altering corticospinal connectivity, and produced long-lasting alterations in the fine motor performance of the adult offspring. Consequences of THC exposure were reminiscent of those elicited by CB1 receptor genetic ablation, and CB1-null mice were resistant to THC-induced alterations. The identity of embryonic THC neuronal targets was determined by a Cre-mediated, lineage-specific, CB1 expression-rescue strategy in a CB1-null background. Early and selective CB1 reexpression in dorsal telencephalic glutamatergic neurons but not forebrain GABAergic neurons rescued the deficits in corticospinal motor neuron development of CB1-null mice and restored susceptibility to THC-induced motor alterations. In addition, THC administration induced an increase in seizure susceptibility that was mediated by its interference with CB1-dependent regulation of both glutamatergic and GABAergic neuron development. These findings demonstrate that prenatal exposure to THC has long-lasting deleterious consequences in the adult offspring solely mediated by its ability to disrupt the neurodevelopmental role of CB1 signaling.

scholarly journals Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex

2015 ◽  
Vol 112 (37) ◽  
pp. 11702-11707 ◽  
Author(s):  
William L. McKenna ◽  
Christian F. Ortiz-Londono ◽  
Thomas K. Mathew ◽  
Kendy Hoang ◽  
Sol Katzman ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Projection Neuron ◽  
Dependent Manner ◽  
Neuron Development ◽  
Cortical Projection ◽  
Expression Of Genes ◽  
Axon Development ◽  
Mutual Regulation ◽  
A Cell ◽  
Cortical Projection Neuron

Generation of distinct cortical projection neuron subtypes during development relies in part on repression of alternative neuron identities. It was reported that the special AT-rich sequence-binding protein 2 (Satb2) is required for proper development of callosal neuron identity and represses expression of genes that are essential for subcerebral axon development. Surprisingly, Satb2 has recently been shown to be necessary for subcerebral axon development. Here, we unravel a previously unidentified mechanism underlying this paradox. We show that SATB2 directly activates transcription of forebrain embryonic zinc finger 2 (Fezf2) and SRY-box 5 (Sox5), genes essential for subcerebral neuron development. We find that the mutual regulation between Satb2 and Fezf2 enables Satb2 to promote subcerebral neuron identity in layer 5 neurons, and to repress subcerebral characters in callosal neurons. Thus, Satb2 promotes the development of callosal and subcerebral neurons in a cell context-dependent manner.

scholarly journals Cited2 Regulates Neocortical Layer II/III Generation and Somatosensory Callosal Projection Neuron Development and Connectivity

2016 ◽  
Vol 36 (24) ◽  
pp. 6403-6419 ◽  
Author(s):  
Ryann M. Fame ◽  
Jessica L. MacDonald ◽  
Sally L. Dunwoodie ◽  
Emi Takahashi ◽  
Jeffrey D. Macklis
Keyword(s):  
Projection Neuron ◽  
Neuron Development ◽  
Callosal Projection

scholarly journals Endocannabinoid signalling in stem cells and cerebral organoids drives differentiation to deep layer projection neurons via CB1 receptors

Development ◽  
2020 ◽  
Vol 147 (24) ◽  
pp. dev192161
Author(s):  
Juan Paraíso-Luna ◽  
José Aguareles ◽  
Ricardo Martín ◽  
Ane C. Ayo-Martín ◽  
Samuel Simón-Sánchez ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Deep Layer ◽  
Embryonic Stem ◽  
Projection Neuron ◽  
Projection Neurons ◽  
Neuron Development ◽  
Receptor Agonists ◽  
Pluripotent Embryonic Stem Cell

ABSTRACTThe endocannabinoid (eCB) system, via the cannabinoid CB1 receptor, regulates neurodevelopment by controlling neural progenitor proliferation and neurogenesis. CB1 receptor signalling in vivo drives corticofugal deep layer projection neuron development through the regulation of BCL11B and SATB2 transcription factors. Here, we investigated the role of eCB signalling in mouse pluripotent embryonic stem cell-derived neuronal differentiation. Characterization of the eCB system revealed increased expression of eCB-metabolizing enzymes, eCB ligands and CB1 receptors during neuronal differentiation. CB1 receptor knockdown inhibited neuronal differentiation of deep layer neurons and increased upper layer neuron generation, and this phenotype was rescued by CB1 re-expression. Pharmacological regulation with CB1 receptor agonists or elevation of eCB tone with a monoacylglycerol lipase inhibitor promoted neuronal differentiation of deep layer neurons at the expense of upper layer neurons. Patch-clamp analyses revealed that enhancing cannabinoid signalling facilitated neuronal differentiation and functionality. Noteworthy, incubation with CB1 receptor agonists during human iPSC-derived cerebral organoid formation also promoted the expansion of BCL11B+ neurons. These findings unveil a cell-autonomous role of eCB signalling that, via the CB1 receptor, promotes mouse and human deep layer cortical neuron development.

scholarly journals Progenitor cell diversity in the developing mouse neocortex

2021 ◽  
Vol 118 (10) ◽  
pp. e2018866118
Author(s):  
Xiangbin Ruan ◽  
Bowei Kang ◽  
Cai Qi ◽  
Wenhe Lin ◽  
Jingshu Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cell ◽  
Developmental Stages ◽  
Marker Gene ◽  
Projection Neuron ◽  
Neural Progenitors ◽  
Neuron Type ◽  
Neuronal Identity ◽  
Cell Diversity ◽  
Type Specification

In the mammalian neocortex, projection neuron types are sequentially generated by the same pool of neural progenitors. How neuron type specification is related to developmental timing remains unclear. To determine whether temporal gene expression in neural progenitors correlates with neuron type specification, we performed single-cell RNA sequencing (scRNA-Seq) analysis of the developing mouse neocortex. We uncovered neuroepithelial cell enriched genes such as Hmga2 and Ccnd1 when compared to radial glial cells (RGCs). RGCs display dynamic gene expression over time; for instance, early RGCs express higher levels of Hes5, and late RGCs show higher expression of Pou3f2. Interestingly, intermediate progenitor cell marker gene Eomes coexpresses temporally with known neuronal identity genes at different developmental stages, though mostly in postmitotic cells. Our results delineate neural progenitor cell diversity in the developing mouse neocortex and support that neuronal identity genes are transcriptionally evident in Eomes-positive cells.

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