scholarly journals Differentiation and localization of interneurons in the developing spinal cord depends on DOT1L expression

2020 ◽  
Author(s):  
Angelica Gray de Cristoforis ◽  
Francesco Ferrari ◽  
Frédéric Clotman ◽  
Tanja Vogel
Keyword(s):  
Spinal Cord ◽  
Neural Tube ◽  
Transcriptional Activation ◽  
Neural Tube Closure ◽  
Epigenetic Factors ◽  
Late Developmental Stage ◽  
Neural Tube Closure Defect ◽  
H3k79 Methylation ◽  
Tube Closure ◽  
Developing Spinal Cord

Abstract Genetic and epigenetic factors contribute to the development of the spinal cord. Failure in correct exertion of the developmental programs, including neurulation, neural tube closure and neurogenesis of the diverse spinal cord neuronal subtypes results in clinical phenotypes with variable severity. The histone methyltransferase Disruptor of Telomeric 1 Like (DOT1L), which mediates histone H3 lysine 79 (H3K79) methylation, is fundamental for proper development of the cerebral cortex and cerebellum, and here we report on its essential role for development of the spinal cord. Conditional inactivation of DOT1L using Wnt1-cre as driver in the developing murine spinal cord did not result in neural tube closure defect (NTCD). Transcriptome analysis revealed that DOT1L deficiency favored differentiation over progenitor proliferation. Dot1l -cKO mainly decreased the numbers of dI1 interneurons expressing Lhx2 . Loss of DOT1L affected localization but not generation of dI2, dI3, and dI5 interneurons. The resulting derailed interneuron patterns might be responsible for increased cell death that occurred at the late developmental stage E18.5. Together our data indicate that DOT1L is essential for subtype- specific neurogenesis, migration and localization of interneurons in the developing spinal cord, in part by regulating transcriptional activation of Lhx2 .

scholarly journals Differentiation and localization of interneurons in the developing spinal cord depends on DOT1L expression

2020 ◽  
Author(s):  
Angelica Gray de Cristoforis ◽  
Francesco Ferrari ◽  
Frédéric Clotman ◽  
Tanja Vogel
Keyword(s):  
Spinal Cord ◽  
Neural Tube ◽  
Transcriptional Activation ◽  
Neural Tube Closure ◽  
Epigenetic Factors ◽  
Late Developmental Stage ◽  
Neural Tube Closure Defect ◽  
H3k79 Methylation ◽  
Tube Closure ◽  
Developing Spinal Cord

Abstract Genetic and epigenetic factors contribute to the development of the spinal cord. Failure in correct exertion of the developmental programs, including neurulation, neural tube closure and neurogenesis of the diverse spinal cord neuronal subtypes results in clinical phenotypes with variable severity. The histone methyltransferase Disruptor of Telomeric 1 Like (DOT1L), which mediates histone H3 lysine 79 (H3K79) methylation, is fundamental for proper development of the cerebral cortex and cerebellum, and here we report on its essential role for development of the spinal cord. Conditional inactivation of DOT1L using Wnt1-cre as driver in the developing murine spinal cord did not result in neural tube closure defect (NTCD). Transcriptome analysis revealed that DOT1L deficiency favored differentiation over progenitor proliferation. Dot1l -cKO mainly decreased the numbers of dI1 interneurons expressing Lhx2 . Loss of DOT1L affected localization but not generation of dI2, dI3, and dI5 interneurons. The resulting derailed interneuron patterns might be responsible for increased cell death that occurred at the late developmental stage E18.5. Together our data indicate that DOT1L is essential for subtype- specific neurogenesis, migration and localization of interneurons in the developing spinal cord, in part by regulating transcriptional activation of Lhx2 .

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.

Cerebral abnormalities in lumbosacral neural tube closure defect: MR imaging evaluation

2001 ◽  
Vol 17 (7) ◽  
pp. 405-410 ◽  
Author(s):  
Tadao Kawamura ◽  
Takato Morioka ◽  
Shunji Nishio ◽  
Futoshi Mihara ◽  
Masashi Fukui
Keyword(s):  
Mr Imaging ◽  
Neural Tube ◽  
Neural Tube Closure ◽  
Imaging Evaluation ◽  
Neural Tube Closure Defect ◽  
Tube Closure

Open brain, a new mouse mutant with severe neural tube defects, shows altered gene expression patterns in the developing spinal cord

Development ◽  
1994 ◽  
Vol 120 (11) ◽  
pp. 3119-3130 ◽  
Author(s):  
T. Gunther ◽  
M. Struwe ◽  
A. Aguzzi ◽  
K. Schughart
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Dorsal Root Ganglia ◽  
Neural Tube ◽  
Dorsal Root ◽  
Expression Patterns ◽  
Axial Skeleton ◽  
Neural Tube Closure ◽  
Primary Defect ◽  
Developing Spinal Cord

We describe a new mouse mutation, designated open brain (opb), which results in severe defects in the developing neural tube. Homozygous opb embryos exhibited an exencephalic malformation involving the forebrain, midbrain and hindbrain regions. The primary defect of the exencephaly could be traced back to a failure to initiate neural tube closure at the midbrain-forebrain boundary. Severe malformations in the spinal cord and dorsal root ganglia were observed in the thoracic region. The spinal cord of opb mutant embryos exhibited an abnormal circular to oval shape and showed defects in both ventral and dorsal regions. In severely affected spinal cord regions, a dorsalmost region of cells negative for Wnt-3a, Msx-2, Pax-3 and Pax-6 gene expression was detected and dorsal expression of Pax-6 was increased. In ventral regions, the area of Shh and HNF-3 beta expression was enlarged and the future motor neuron horns appeared to be reduced in size. These observations indicate that opb embryos exhibit defects in the specification of cells along the dorsoventral axis of the developing spinal cord. Although small dorsal root ganglia were formed in opb mutants, their metameric organization was lost. In addition, defects in eye development and malformations in the axial skeleton and developing limbs were observed. The implications of these findings are discussed in the context of dorsoventral patterning of the developing neural tube and compared with known mouse mutants exhibiting similar defects.

scholarly journals ANENCEPHALIC FETUS WITH CRANIOSPINAL RACHISCHISIS – CASE REPORT

2021 ◽  
Vol 9 (5) ◽  
pp. 24-29
Author(s):  
Ayse Konac
Keyword(s):  
Spinal Cord ◽  
Neural Tube ◽  
Unusual Case ◽  
First Trimester ◽  
Economic Life ◽  
Neural Tube Closure ◽  
Substantial Part ◽  
Predisposing Factor ◽  
The Brain ◽  
Tube Closure

Anencephaly, in which a substantial part of the brain, skull, or scalp is missing, is a lethal neural tube defect (NTD) that occurs during the fourth week of pregnancy after failed cranial neuropore closure. One in every 1,000 births is anencephalic, and newborns with this NTD are not viable or treatable. Associated with anencephaly is rachischisis, or severe incomplete neural tube closure and exposure of the spinal cord. Ultrasonography can quickly diagnose anencephaly. Like other NTDs, nutritional and environmental factors both play a role in the development of anencephaly. Here, we report and discuss an unusual case of a 12-week gestation anencephalic fetus with craniospinal rachischisis and its embryological roots. In our case, except from the low socio-economic life of the patient, the absence of a predisposing factor that could cause such an anomaly, the abortion being in the first trimester and the occurrence in the first pregnancy of the patient as a result of 5-year infertility made us think that pathology examination of the abortus material is important in complet or incomplete abortions.

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