scholarly journals Human spinal cord organoids exhibiting neural tube morphogenesis for a quantifiable drug screening system of neural tube defects

2020 ◽  
Author(s):  
Ju-Hyun Lee ◽  
Hyogeun Shin ◽  
Mohammed R. Shaker ◽  
Hyun Jung Kim ◽  
June Hoan Kim ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Disease Modeling ◽  
Motor Behavior ◽  
Scale Up ◽  
3D Culture ◽  
Spinal Cord Neurons ◽  
Human Spinal Cord ◽  
Spinal Cord Development

AbstractThe human spinal cord forms well-organized neural circuits for environment sensing and motor behavior. The three-dimensional (3D) induction of the spinal cord-like tissue from human pluripotent stem cells has been reported, but they often do not mimic morphological features of neurulation and their maturity is limited. Here, we report an advanced 3D culture system for the production of human spinal cord-like organoids (hSCOs) suitable for the scale-up and quantitative studies. The hSCOs exhibited many aspects of spinal cord development, including neurulation-like tube-forming morphogenesis, differentiation of the major spinal cord neurons and glial cells, and mature synaptic functional activities. We further demonstrated that hSCOs platform allowed quantitative and systematic high-throughput examination of the potential risk of neural tube defects induced by antiepileptic drugs. Thus, hSCOs can be used for understanding human spinal cord development, disease modeling, and toxicology screening.

The control of rostrocaudal pattern in the developing spinal cord: specification of motor neuron subtype identity is initiated by signals from paraxial mesoderm

Development ◽  
1998 ◽  
Vol 125 (6) ◽  
pp. 969-982 ◽  
Author(s):  
M. Ensini ◽  
T.N. Tsuchida ◽  
H.G. Belting ◽  
T.M. Jessell
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Neural Tube ◽  
Motor Behavior ◽  
Neural Tube Closure ◽  
Paraxial Mesoderm ◽  
Homeodomain Protein ◽  
Mesodermal Cell ◽  
Developing Spinal Cord

The generation of distinct classes of motor neurons is an early step in the control of vertebrate motor behavior. To study the interactions that control the generation of motor neuron subclasses in the developing avian spinal cord we performed in vivo grafting studies in which either the neural tube or flanking mesoderm were displaced between thoracic and brachial levels. The positional identity of neural tube cells and motor neuron subtype identity was assessed by Hox and LIM homeodomain protein expression. Our results show that the rostrocaudal identity of neural cells is plastic at the time of neural tube closure and is sensitive to positionally restricted signals from the paraxial mesoderm. Such paraxial mesodermal signals appear to control the rostrocaudal identity of neural tube cells and the columnar subtype identity of motor neurons. These results suggest that the generation of motor neuron subtypes in the developing spinal cord involves the integration of distinct rostrocaudal and dorsoventral patterning signals that derive, respectively, from paraxial and axial mesodermal cell groups.

Chronic Deafferentation of Human Spinal Cord Neurons

1968 ◽  
Vol 29 (1) ◽  
pp. 48-50 ◽  
Author(s):  
John D. Loeser ◽  
Arthur A. Ward ◽  
Lowell E. White
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Neurons ◽  
Human Spinal Cord

scholarly journals Analysis of the effects of Streptomyces hyaluronidase on formation of the neural tube

Development ◽  
1983 ◽  
Vol 73 (1) ◽  
pp. 1-15
Author(s):  
Gary C. Schoenwolf ◽  
Marilyn Fisher
Keyword(s):  
Spinal Cord ◽  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Developmental Process ◽  
Chick Embryos ◽  
In Ovo ◽  
Dorsal Midline ◽  
Specific Protease

Chick embryos at stages 8 to 9 were treated in ovo with Streptomyces hyaluronidase (SH) to determine whether neurulation occurs normally in embryos depleted of hyaluronic acid, a major component of the extracellular matrix. Open neural tube defects occurred in 60–94 % (depending on the particular enzyme batch) of the embryos treated with SH and examined after an additional 24 h of incubation. Defects were confined mainly to the spinal cord. The neural folds underwent elevation in defective regions but failed to converge and fuse across the dorsal midline. The extracellular matrix of embryos treated with SH was depleted consistently, as determined with sections stained with Alcian blue. Control experiments were done to ensure that neural tube defects were not caused by non-specific protease contamination of SH, or by digestion products of hyaluronic acid. We propose several plausible and testable mechanisms through which the extracellular matrix might influence the complex developmental process of neurulation.

scholarly journals FZD10 regulates cell proliferation and mediates Wnt1 induced neurogenesis in the developing spinal cord

2019 ◽  
Author(s):  
Abdulmajeed Fahad Alrefaei ◽  
Andrea E. Münsterberg ◽  
Grant N. Wheeler
Keyword(s):  
Spinal Cord ◽  
Cell Proliferation ◽  
Neural Tube ◽  
Spinal Cord Development ◽  
Dorsal Neural Tube ◽  
Wnt Ligands ◽  
Frizzled Receptors ◽  
Developmental Contexts ◽  
Developing Spinal Cord

AbstractWnt/FZD signalling activity is required for spinal cord development, including the dorsal-ventral patterning of the neural tube, where it affects proliferation and specification of neurons. Wnt ligands initiate canonical, β-catenin-dependent, signaling by binding to Frizzled receptors. However, in many developmental contexts the cognate FZD receptor for a particular Wnt ligand remains to be identified. Here, we characterized FZD10 expression in the dorsal neural tube where it overlaps with both Wnt1 and Wnt3a, as well as markers of dorsal progenitors and interneurons. We show FZD10 expression is sensitive to Wnt1, but not Wnt3a expression, and FZD10 plays a role in neural tube patterning. Knockdown approaches show that Wnt1 induced ventral expansion of dorsal neural markes, Pax6 and Pax7, requires FZD10. In contrast, Wnt3a induced dorsalization of the neural tube is not affected by FZD10 knockdown. Gain of function experiments show that FZD10 is not sufficient on its own to mediate Wnt1 activity in vivo. Indeed excess FZD10 inhibits the dorsalizing activity of Wnt1. However, addition of the Lrp6 co-receptor dramatically enhances the Wnt1/FZD10 mediated activation of dorsal markers. This suggests that the mechanism by which Wnt1 regulates proliferation and patterning in the neural tube requires both FZD10 and Lrp6.

Spina Bifida and Related Conditions

2017 ◽  
Author(s):  
Stephen L. Kinsman
Keyword(s):  
Spinal Cord ◽  
Spina Bifida ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Spinal Dysraphism ◽  
Gene Interactions ◽  
Tethered Spinal Cord ◽  
Spinal Lesion ◽  
Gene Environment ◽  
Spina Bifida Aperta

The term “spinal dysraphism” encompasses the broadest array of the conditions known as the neural tube defects. The open neural tube defects (spina bifida aperta and cystica) include both disorders of primary and/or secondary neuralation and are best defined as myelomeningocele complex (MMC) due to their protean nervous system manifestations beyond the spinal lesion. Closed spinal dysraphisms (so-called spina bifida occulta) include lipomatous lesions, forms of tethered spinal cord, sinus tracts, and forms of split spinal cord (diastematomyelia). Both genetic and environmental etiologies have been identified. Gene-environment and gene-gene interactions are also important in the pathobiology of these conditions.

scholarly journals Bilobed Thoracic Meningomyelocele: A Case Report with Literature Review

2019 ◽  
Vol 16 (1) ◽  
pp. 39-41
Author(s):  
Dipendra Shrestha ◽  
Binod Rajbhandari ◽  
Sushil Krishna Shilpakar
Keyword(s):  
Spinal Cord ◽  
Case Report ◽  
Literature Review ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Congenital Malformations ◽  
Rare Case ◽  
Brain And Spinal Cord ◽  
The Brain

Neural tube defects (NTDs) arethe most common congenital malformations affecting the brain and spinal cord. Furthermore, meningomyelocele (MMC) is said to be one of the commonest NTDs. Multiple MMC is uncommon and bilobed sac is even rarer, comparatively. In literature, only few such cases have been reported. Here, we present a rare case of bilobed thoracic MMC operated successfully in our department.

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