scholarly journals Simultaneous production of diverse neuronal subtypes during early corticogenesis

2018 ◽  
Author(s):  
E. Magrinelli ◽  
R. J. Wagener ◽  
D. Jabaudon
Keyword(s):  
Deep Layer ◽  
Ventricular Zone ◽  
Neuronal Cell ◽  
Cell Types ◽  
Superficial Layer ◽  
High Temporal Resolution ◽  
Fine Grained ◽  
Molecular Identity ◽  
Deep Layers ◽  
Successive Generations

AbstractThe circuits of the neocortex are composed of a broad diversity of neuronal cell types, which can be distinguished by their laminar location, molecular identity, and connectivity. During embryogenesis, successive generations of glutamatergic neurons are sequentially born from progenitors located in germinal zones below the cortex. In this process, the earliest-born generations of neurons differentiate to reside in deep layers, while later-born daughter neurons reside in more superficial layers. Although the aggregate competence of progenitors to produce successive subtypes of neurons progresses as corticogenesis proceeds, a fine-grained temporal understanding of how neuronal subtypes are sequentially produced is still missing. Here, we use FlashTag, a high temporal resolution labeling approach, to follow the fate of the simultaneously-born daughter neurons of ventricular zone progenitors at multiple stages of corticogenesis. Our findings reveal a bimodal regulation in the diversity of neurons being produced at single time points of corticogenesis. Initially, distinct subtypes of deep-layer neurons are simultaneously produced, as defined by their laminar location, molecular identity and connectivity. Later on, instead, instantaneous neuronal production is homogeneous and the distinct superficial-layer neurons subtypes are sequentially produced. These findings suggest that early-born, deep-layer neurons have a less determined fate potential than later-born superficial layer neurons, which may reflect the progressive implementation of pre-and/or post-mitotic mechanisms controlling neuronal fate reliability.

scholarly journals Task-specific differences in respiration-related activation of deep and superficial pelvic floor muscles

2019 ◽  
Vol 126 (5) ◽  
pp. 1343-1351 ◽  
Author(s):  
Rafeef Aljuraifani ◽  
Ryan E. Stafford ◽  
Leanne M. Hall ◽  
Wolbert van den Hoorn ◽  
Paul W. Hodges
Keyword(s):  
Pelvic Floor ◽  
Deep Layer ◽  
Pelvic Floor Dysfunction ◽  
Muscle Layer ◽  
Superficial Layer ◽  
Pelvic Floor Muscles ◽  
Abdominal Pressure ◽  
Quiet Breathing ◽  
Abdominal Organs ◽  
Deep Layers

The female pelvic floor muscles (PFM) are arranged in distinct superficial and deep layers that function to support the pelvic/abdominal organs and maintain continence, but with some potential differences in function. Although general recordings of PFM activity show amplitude modulation in conjunction with fluctuation in intra-abdominal pressure such as that associated with respiration, it is unclear whether the activities of the two PFM layers modulate in a similar manner. This study aimed to investigate the activation of the deep and superficial PFM during a range of respiratory tasks in different postures. Twelve women without pelvic floor dysfunction participated. A custom-built surface electromyography (EMG) electrode was used to record the activation of the superficial and deep PFM during quiet breathing, breathing with increased dead space, coughing, and maximal and submaximal inspiratory and expiratory efforts. As breathing demand increased, the deep PFM layer EMG had greater coherence with respiratory airflow at the frequency of respiration than the superficial PFM ( P = 0.038). During cough, the superficial PFM activated earlier than the deep PFM in the sitting position ( P = 0.043). In contrast, during maximal and submaximal inspiratory and expiratory efforts, the superficial PFM EMG was greater than that for the deep PFM ( P = 0.011). These data show that both layers of PFM are activated during both inspiration and expiration, but with a bias to greater activation in expiratory tasks/phases. Activation of the deep and superficial PFM layers differed in most of the respiratory tasks, but there was no consistent bias to one muscle layer.NEW & NOTEWORTHY Although pelvic floor muscles are generally considered as a single entity, deep and superficial layers have different anatomies and biomechanics. Here we show task-specific differences in recruitment between layers during respiratory tasks in women. The deep layer was more tightly modulated with respiration than the superficial layer, but activation of the superficial layer was greater during maximal/submaximal occluded respiratory efforts and earlier during cough. These data highlight tightly coordinated recruitment of discrete pelvic floor muscles for respiration.

scholarly journals Single-cell transcriptional dynamics and origins of neuronal diversity in the developing mouse neocortex

2018 ◽  
Author(s):  
L. Telley ◽  
G. Agirman ◽  
J. Prados ◽  
S. Fièvre ◽  
P. Oberst ◽  
...  
Keyword(s):  
Single Cell ◽  
Neuronal Cell ◽  
Cell Types ◽  
Neuronal Diversity ◽  
Glutamatergic Neurons ◽  
Transcriptional Dynamics ◽  
Mouse Cerebral Cortex ◽  
Differentiation Stage ◽  
Newborn Neurons ◽  
Successive Generations

During cortical development, distinct subtypes of glutamatergic neurons are sequentially born and differentiate from dynamic populations of progenitors. The neurogenic competence of these progenitors progresses as corticogenesis proceeds; likewise, newborn neurons transit through sequential states as they differentiate. Here, we trace the developmental transcriptional trajectories of successive generations of apical progenitors (APs) and isochronic cohorts of their daughter neurons using parallel single-cell RNA sequencing between embryonic day (E) 12 and E15 in the mouse cerebral cortex. Our results identify the birthdate- and differentiation stage-related transcriptional dynamics at play during corticogenesis. As corticogenesis proceeds, APs transit through embryonic age-dependent molecular states, which are transmitted to their progeny to generate successive initial daughter cell identities. In neurons, essentially conserved post-mitotic differentiation programs are applied onto these distinct AP-derived ground states, allowing temporally-regulated sequential emergence of specialized neuronal cell types. Molecular temporal patterning of sequentially-born daughter neurons by their respective mother cell thus underlies emergence of neuronal diversity in the neocortex.One Sentence SummaryDuring corticogenesis, temporally dynamic molecular birthmarks are transmitted from progenitors to their post-mitotic progeny to generate neuronal diversity.

The lateral wall of the cavernous sinus

1982 ◽  
Vol 56 (2) ◽  
pp. 228-234 ◽  
Author(s):  
Felix Umansky ◽  
Hilel Nathan
Keyword(s):  
Cavernous Sinus ◽  
Deep Layer ◽  
Lateral Wall ◽  
Superficial Layer ◽  
Content Type ◽  
Deep Layers ◽  
Fine Print

✓ In a study of the cavernous sinus in 70 specimens, the lateral wall of the sinus was found to be formed by two layers: a superficial, dural layer and a deep layer. The latter was formed by the sheaths of nerves III, IV, and V1,2 plus a reticular membrane extending between the sheaths. This membrane was often incomplete, particularly beween the sheaths of nerves III and IV above, and V1 below. These findings do not conform with the descriptions of a single dural layer of the lateral wall, with nerves III, IV, and V1,2 embedded in it, nor to other descriptions showing the cavity of the sinus divided into two compartments by a septum close to the lateral wall, with nerves III, IV, and V1 located within the septum. In the present study, the superficial and the deep layers of the lateral wall were found to be loosely attached to each other and easy to separate. In no case was a superficial compartment of the sinus found to be present between the two layers, and the nerves were never found to be running embedded in the superficial layer.

scholarly journals Apical progenitors remain multipotent throughout cortical neurogenesis

2018 ◽  
Author(s):  
Polina Oberst ◽  
Sabine Fièvre ◽  
Natalia Baumann ◽  
Cristina Concetti ◽  
Denis Jabaudon
Keyword(s):  
Ventricular Zone ◽  
Superficial Layer ◽  
High Temporal Resolution ◽  
Fate Map ◽  
Pulse Label ◽  
Intermediate Progenitors ◽  
Multipotent Cells ◽  
Cell Type Specific ◽  
Temporal Identity ◽  
Fate Restriction

The diverse subtypes of excitatory neurons that populate the neocortex are born from progenitors located in the ventricular zone (apical progenitors, APs). During corticogenesis, APs progress through successive temporal states to sequentially generate deep- followed by superficial-layer neurons directly or via the generation of intermediate progenitors (IPs). Yet little is known about the plasticity of AP temporal identity and whether individual progenitor subtypes remain multipotent throughout corticogenesis. To address this question, we used FlashTag (FT), a method to pulse-label and isolate APs in the mouse neocortex with high temporal resolution to fate-map neuronal progeny following heterochronic transplantation of APs into younger embryos. We find that unlike daughter IPs, which lose the ability to generate deep layer neurons when transplanted into a younger host, APs are temporally uncommitted and become molecularly respecified to generate normally earlier-born neuron types. These results indicate that APs are multipotent cells that are able to revert their temporal identity and re-enter past molecular and neurogenic states. AP fate progression thus occurs without detectable fate restriction during the neurogenic period of corticogenesis. These findings identify unforeseen cell-type specific differences in cortical progenitor fate plasticity, which could be exploited for neuroregenerative purposes.

Diversity and excitability of deep-layer entorhinal cortical neurons in a model of temporal lobe epilepsy

2012 ◽  
Vol 108 (6) ◽  
pp. 1724-1738 ◽  
Author(s):  
Jyotsna Pilli ◽  
Saad Abbasi ◽  
Max Richardson ◽  
Sanjay S. Kumar
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Cortical Neurons ◽  
Deep Layer ◽  
Superficial Layer ◽  
Electrophysiological Properties ◽  
Epileptiform Discharges ◽  
Layer Neuron ◽  
Excitatory Neurons ◽  
Deep Layers

The entorhinal cortex (ERC) is critically implicated in temporal lobe epileptogenesis—the most common type of adult epilepsy. Previous studies have suggested that epileptiform discharges likely initiate in seizure-sensitive deep layers (V–VI) of the medial entorhinal area (MEA) and propagate into seizure-resistant superficial layers (II–III) and hippocampus, establishing a lamina-specific distinction between activities of deep- versus superficial-layer neurons and their seizure susceptibilities. While layer II stellate cells in MEA have been shown to be hyperexcitable and hypersynchronous in patients and animal models of temporal lobe epilepsy (TLE), the fate of neurons in the deep layers under epileptic conditions and their overall contribution to epileptogenicity of this region have remained unclear. We used whole cell recordings from slices of the ERC in normal and pilocarpine-treated epileptic rats to characterize the electrophysiological properties of neurons in this region and directly assess changes in their excitatory and inhibitory synaptic drive under epileptic conditions. We found a surprising heterogeneity with at least three major types and two subtypes of functionally distinct excitatory neurons. However, contrary to expectation, none of the major neuron types characterized showed any significant changes in their excitability, barring loss of excitatory and inhibitory inputs in a subtype of neurons whose dendrite extended into layer III, where neurons are preferentially lost during TLE. We confirmed hyperexcitability of layer II neurons in the same slices, suggesting minimal influence of deep-layer input on superficial-layer neuron excitability under epileptic conditions. These data show that deep layers of ERC contain a more diverse population of excitatory neurons than previously envisaged that appear to belie their seizure-sensitive reputation.

scholarly journals Temporal patterning of apical progenitors and their daughter neurons in the developing neocortex

Science ◽  
2019 ◽  
Vol 364 (6440) ◽  
pp. eaav2522 ◽  
Author(s):  
L. Telley ◽  
G. Agirman ◽  
J. Prados ◽  
N. Amberg ◽  
S. Fièvre ◽  
...  
Keyword(s):  
Ventricular Zone ◽  
Mouse Embryos ◽  
High Temporal Resolution ◽  
Neuronal Diversity ◽  
Core Set ◽  
Evolutionarily Conserved ◽  
Repressor Complex ◽  
Age Dependent ◽  
Developing Neocortex ◽  
Successive Generations

During corticogenesis, distinct subtypes of neurons are sequentially born from ventricular zone progenitors. How these cells are molecularly temporally patterned is poorly understood. We used single-cell RNA sequencing at high temporal resolution to trace the lineage of the molecular identities of successive generations of apical progenitors (APs) and their daughter neurons in mouse embryos. We identified a core set of evolutionarily conserved, temporally patterned genes that drive APs from internally driven to more exteroceptive states. We found that the Polycomb repressor complex 2 (PRC2) epigenetically regulates AP temporal progression. Embryonic age–dependent AP molecular states are transmitted to their progeny as successive ground states, onto which essentially conserved early postmitotic differentiation programs are applied, and are complemented by later-occurring environment-dependent signals. Thus, epigenetically regulated temporal molecular birthmarks present in progenitors act in their postmitotic progeny to seed adult neuronal diversity.

scholarly journals The landscape of alternative polyadenylation in single cells of the developing mouse embryo

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Vikram Agarwal ◽  
Sereno Lopez-Darwin ◽  
David R. Kelley ◽  
Jay Shendure
Keyword(s):  
Rna Binding ◽  
Developmental Stages ◽  
Single Cells ◽  
Neuronal Cell ◽  
Alternative Polyadenylation ◽  
Cell Types ◽  
Untranslated Regions ◽  
Mammalian Development ◽  
Translation Rate ◽  
Dynamic Landscape

Abstract3′ untranslated regions (3′ UTRs) post-transcriptionally regulate mRNA stability, localization, and translation rate. While 3′-UTR isoforms have been globally quantified in limited cell types using bulk measurements, their differential usage among cell types during mammalian development remains poorly characterized. In this study, we examine a dataset comprising ~2 million nuclei spanning E9.5–E13.5 of mouse embryonic development to quantify transcriptome-wide changes in alternative polyadenylation (APA). We observe a global lengthening of 3′ UTRs across embryonic stages in all cell types, although we detect shorter 3′ UTRs in hematopoietic lineages and longer 3′ UTRs in neuronal cell types within each stage. An analysis of RNA-binding protein (RBP) dynamics identifies ELAV-like family members, which are concomitantly induced in neuronal lineages and developmental stages experiencing 3′-UTR lengthening, as putative regulators of APA. By measuring 3′-UTR isoforms in an expansive single cell dataset, our work provides a transcriptome-wide and organism-wide map of the dynamic landscape of alternative polyadenylation during mammalian organogenesis.

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