scholarly journals Symmetry breaking of hPSCs in micropattern generates a polarized spinal cord-like organoid (pSCO) with dorsoventral organization

2021 ◽  
Author(s):  
Kyubin Seo ◽  
Subin Cho ◽  
Ju-Hyun Lee ◽  
June Hoan Kim ◽  
Boram Lee ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cell Differentiation ◽  
Symmetry Breaking ◽  
Neural Development ◽  
Early Embryo ◽  
Cell Patterning ◽  
Axis Formation ◽  
Brain Structure And Function ◽  
Brain Organoid ◽  
And Function

Brain organoid research is advancing, but generation of organoids with proper axis formation, which could lead to spatially ordered structures for complex brain structure and function, still remains a challenge. Axis formation and related spatial cell organization in the CNS are initiated by the symmetry breaking during the early embryo development. It has been demonstrated that the geometrically confined culture of human pluripotent stem cells (hPSCs) can be used to induce symmetry breaking and regionalized cell differentiation. In this study, we generated a polarized spinal cord organoid with a self-organized dorsoventral (DV) organization, using 2D cell patterning by geometric confinement. Initially, the application of caudalization signals to hPSCs promoted the regionalized cell differentiation along the radial axis and sprouting-like protrusion morphogenesis in cell colonies confined to ECM protein micropatterns. Detachment of colonies turned them into extended spinal cord-like organoids which maintained center- and edge-derived two poles. Further analyses including single cell RNA sequencing and spatial transcriptome analysis unveiled that these organoids contained rich repertoire of developing spinal cord cells and exhibited the spatially ordered DV domain formation along the long axis without external organizing signals. Modulation of BMP and Shh signaling can control the extent of DV coverage in organoids following the principles of embryo patterning. Our study provides a simple, and precisely controllable method to generate spatially-ordered organoids for understanding of biological principles of cell patterning and axis formation during neural development.

scholarly journals Importance of brain alterations in spinal cord injury

2021 ◽  
Vol 104 (3) ◽  
pp. 003685042110311
Author(s):  
Can Zhao ◽  
Shu-Sheng Bao ◽  
Meng Xu ◽  
Jia-Sheng Rao
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cerebral Cortex ◽  
Information Flow ◽  
Brain Structure ◽  
Structure And Function ◽  
Cord Injury ◽  
Brain Structure And Function ◽  
And Function ◽  
The Brain

Spinal cord injury (SCI) destroys the sensorimotor pathway and blocks the information flow between the peripheral nerve and the brain, resulting in autonomic function loss. Numerous studies have explored the effects of obstructed information flow on brain structure and function and proved the extensive plasticity of the brain after SCI. Great progress has also been achieved in therapeutic strategies for SCI to restore the “re-innervation” of the cerebral cortex to the limbs to some extent. Although no thorough research has been conducted, the changes of brain structure and function caused by “re-domination” have been reported. This article is a review of the recent research progress on local structure, functional changes, and circuit reorganization of the cerebral cortex after SCI. Alterations of structure and electrical activity characteristics of brain neurons, features of brain functional reorganization, and regulation of brain functions by reconfigured information flow were also explored. The integration of brain function is the basis for the human body to exercise complex/fine movements and is intricately and widely regulated by information flow. Hence, its changes after SCI and treatments should be considered.

scholarly journals Could Perinatal Asphyxia Induce a Synaptopathy? New Highlights from an Experimental Model

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
María Inés Herrera ◽  
Matilde Otero-Losada ◽  
Lucas Daniel Udovin ◽  
Carlos Kusnier ◽  
Rodolfo Kölliker-Frers ◽  
...  
Keyword(s):  
Experimental Model ◽  
Neural Development ◽  
Neurological Disorders ◽  
Perinatal Asphyxia ◽  
Birth Asphyxia ◽  
Synaptic Connectivity ◽  
Synaptic Dysfunction ◽  
Preterm Neonates ◽  
Brain Structure And Function ◽  
And Function

Birth asphyxia also termed perinatal asphyxia is an obstetric complication that strongly affects brain structure and function. Central nervous system is highly susceptible to oxidative damage caused by perinatal asphyxia while activation and maturity of the proper pathways are relevant to avoiding abnormal neural development. Perinatal asphyxia is associated with high morbimortality in term and preterm neonates. Although several studies have demonstrated a variety of biochemical and molecular pathways involved in perinatal asphyxia physiopathology, little is known about the synaptic alterations induced by perinatal asphyxia. Nearly 25% of the newborns who survive perinatal asphyxia develop neurological disorders such as cerebral palsy and certain neurodevelopmental and learning disabilities where synaptic connectivity disturbances may be involved. Accordingly, here we review and discuss the association of possible synaptic dysfunction with perinatal asphyxia on the basis of updated evidence from an experimental model.

Centrosome Aurora A gradient ensures single polarity axis in C. elegans embryos

2020 ◽  
Vol 48 (3) ◽  
pp. 1243-1253 ◽  
Author(s):  
Sukriti Kapoor ◽  
Sachin Kotak
Keyword(s):  
Symmetry Breaking ◽  
Cell Fate ◽  
Cell Cortex ◽  
Axis Formation ◽  
Aurora A Kinase ◽  
Aurora A ◽  
C Elegans ◽  
Cell Embryo ◽  
Polarity Establishment

Cellular asymmetries are vital for generating cell fate diversity during development and in stem cells. In the newly fertilized Caenorhabditis elegans embryo, centrosomes are responsible for polarity establishment, i.e. anterior–posterior body axis formation. The signal for polarity originates from the centrosomes and is transmitted to the cell cortex, where it disassembles the actomyosin network. This event leads to symmetry breaking and the establishment of distinct domains of evolutionarily conserved PAR proteins. However, the identity of an essential component that localizes to the centrosomes and promotes symmetry breaking was unknown. Recent work has uncovered that the loss of Aurora A kinase (AIR-1 in C. elegans and hereafter referred to as Aurora A) in the one-cell embryo disrupts stereotypical actomyosin-based cortical flows that occur at the time of polarity establishment. This misregulation of actomyosin flow dynamics results in the occurrence of two polarity axes. Notably, the role of Aurora A in ensuring a single polarity axis is independent of its well-established function in centrosome maturation. The mechanism by which Aurora A directs symmetry breaking is likely through direct regulation of Rho-dependent contractility. In this mini-review, we will discuss the unconventional role of Aurora A kinase in polarity establishment in C. elegans embryos and propose a refined model of centrosome-dependent symmetry breaking.

Improved Beta-Cell Differentiation and Function in Isolated Islets Established in Dynamic Culture to Reduce Hypoxia

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 303-LB
Author(s):  
NAJWA A. AL-JAHDHAMI ◽  
SCOTT J. ANDERSON ◽  
ALI ALDIBBIAT ◽  
JAMES A. SHAW
Keyword(s):  
Cell Differentiation ◽  
Beta Cell ◽  
Isolated Islets ◽  
Dynamic Culture ◽  
And Function

The ENIGMA Brain Injury Working Group: Approach, Challenges, and Potential Benefits

2019 ◽  
Author(s):  
Elisabeth A. Wilde ◽  
Emily L. Dennis ◽  
David F Tate
Keyword(s):  
Brain Injury ◽  
Working Group ◽  
Meta Analysis ◽  
Special Issue ◽  
Group Approach ◽  
Challenges And Opportunities ◽  
Brain Structure And Function ◽  
Potential Benefits ◽  
And Function ◽  
Neuroimaging Genetics

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium brings together researchers from around the world to try to identify the genetic underpinnings of brain structure and function, along with robust, generalizable effects of neurological and psychiatric disorders. The recently-formed ENIGMA Brain Injury working group includes 8 subgroups, based largely on injury mechanism and patient population. This introduction to the special issue summarizes the history, organization, and objectives of ENIGMA Brain Injury, and includes a discussion of strategies, challenges, opportunities and goals common across 6 of the subgroups under the umbrella of ENIGMA Brain Injury. The following articles in this special issue, including 6 articles from different subgroups, will detail the challenges and opportunities specific to each subgroup.

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