scholarly journals Corticothalamic Projection Neuron Development beyond Subtype Specification: Fog2 and Intersectional Controls Regulate Intraclass Neuronal Diversity

Neuron ◽  
2016 ◽  
Vol 91 (1) ◽  
pp. 90-106 ◽  
Author(s):  
Maria J. Galazo ◽  
Jason G. Emsley ◽  
Jeffrey D. Macklis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
I. De Toma ◽  
M. Ortega ◽  
S. Catuara-Solarz ◽  
C. Sierra ◽  
E. Sabidó ◽  
...  

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.



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


2015 ◽  
Vol 112 (44) ◽  
pp. 13693-13698 ◽  
Author(s):  
Adán de Salas-Quiroga ◽  
Javier Díaz-Alonso ◽  
Daniel García-Rincón ◽  
Floortje Remmers ◽  
David Vega ◽  
...  

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.



2015 ◽  
Vol 112 (37) ◽  
pp. 11702-11707 ◽  
Author(s):  
William L. McKenna ◽  
Christian F. Ortiz-Londono ◽  
Thomas K. Mathew ◽  
Kendy Hoang ◽  
Sol Katzman ◽  
...  

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.



2019 ◽  
Author(s):  
Liang Li ◽  
Yajie Tang ◽  
Leqiang Sun ◽  
Jinsong Yu ◽  
Hui Gong ◽  
...  

AbstractThe elegant functions of the brain are facilitated by sophisticated connections between neurons, the architecture of which is frequently characterized by one nucleus connecting to multiple targets via projection neurons. Delineating the sub-nucleus fine architecture of projection neurons in a certain nucleus could greatly facilitate its circuit, computational, and functional resolution. Here, we developed multi-fluorescent rabies virus to delineate the fine organization of corticothalamic projection neuron subsets in the primary visual cortex (V1). By simultaneously labeling multiple distinct subsets of corticothalamic projection neurons in V1 from their target nuclei in thalamus (dLGN, LP, LD), we observed that V1-dLGN corticothalamic neurons were densely concentrated in layer VI, except for several sparsely scattered neurons in layer V, while V1-LP and V1-LD corticothalamic neurons were localized to both layers V and VI. Meanwhile, we observed a fraction of V1 corticothalamic neurons targeting multiple thalamic nuclei, which was further confirmed by fMOST whole-brain imaging. We further conceptually proposed an upgraded sub-nucleus tracing system with higher throughput (21 subsets) for more complex architectural tracing. The multi-fluorescent RV tracing tool can be extensively applied to resolve architecture of projection neuron subsets, with a strong potential to delineate the computational and functional organization of these nuclei.



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


Development ◽  
2020 ◽  
Vol 147 (24) ◽  
pp. dev192161
Author(s):  
Juan Paraíso-Luna ◽  
José Aguareles ◽  
Ricardo Martín ◽  
Ane C. Ayo-Martín ◽  
Samuel Simón-Sánchez ◽  
...  

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.



2010 ◽  
Vol 28 (8) ◽  
pp. 688-688
Author(s):  
R.F. Hevner ◽  
F. Bedogni ◽  
R.D. Hodge ◽  
G.E. Elsen ◽  
B.R. Nelson ◽  
...  


2017 ◽  
Vol 80 ◽  
pp. 44-51 ◽  
Author(s):  
R.R. Waclaw ◽  
L.A. Ehrman ◽  
P. Merchan-Sala ◽  
V. Kohli ◽  
D. Nardini ◽  
...  


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