Hoxd10 induction and regionalization in the developing lumbosacral spinal cord

Development ◽  
2001 ◽  
Vol 128 (12) ◽  
pp. 2255-2268 ◽  
Author(s):  
Cynthia Lance-Jones ◽  
Natalia Omelchenko ◽  
Anya Bailis ◽  
Stephen Lynch ◽  
Kamal Sharma
Keyword(s):  
Spinal Cord ◽  
Neural Tube ◽  
Neural Tube Closure ◽  
Paraxial Mesoderm ◽  
Lumbosacral Region ◽  
Environmental Signals ◽  
Lumbosacral Spinal Cord ◽  
Column Formation ◽  
Lim Proteins ◽  
High Level

We have used Hoxd10 expression as a primary marker of the lumbosacral region to examine the early programming of regional characteristics within the posterior spinal cord of the chick embryo. Hoxd10 is uniquely expressed at a high level in the lumbosacral cord, from the earliest stages of motor column formation through stages of motoneuron axon outgrowth. To define the time period when this gene pattern is determined, we assessed Hoxd10 expression after transposition of lumbosacral and thoracic segments at early neural tube stages. We present evidence that there is an early prepattern for Hoxd10 expression in the lumbosacral neural tube; a prepattern that is established at or before stages of neural tube closure. Cells within more posterior lumbosacral segments have a greater ability to develop high level Hoxd10 expression than the most anterior lumbosacral segments or thoracic segments. During subsequent neural tube stages, this prepattern is amplified and stabilized by environmental signals such that all lumbosacral segments acquire the ability to develop high levels of Hoxd10, independent of their axial environment. Results from experiments in which posterior neural segments and/or paraxial mesoderm segments were placed at different axial levels suggest that signals setting Hoxd10 expression form a decreasing posterior-to-anterior gradient. Our experiments do not, however, implicate adjacent paraxial mesoderm as the only source of graded signals. We suggest, instead, that signals from more posterior embryonic regions influence Hoxd10 expression after the early establishment of a regional prepattern. Concurrent analyses of patterns of LIM proteins and motor column organization after experimental surgeries suggest that the programming of these characteristics follows similar rules.

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.

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 Pax3acts cell autonomously in the neural tube and somites by controlling cell surface properties

Development ◽  
2001 ◽  
Vol 128 (11) ◽  
pp. 1995-2005 ◽  
Author(s):  
Ahmed Mansouri ◽  
Patrick Pla ◽  
Lionel Larue ◽  
Peter Gruss
Keyword(s):  
Cell Surface ◽  
Neural Crest ◽  
Surface Properties ◽  
Neural Tube ◽  
Es Cells ◽  
Embryonic Stem ◽  
Neural Tube Closure ◽  
Paraxial Mesoderm ◽  
Wild Type ◽  
Cell Surface Properties

Pax3 is a member of the paired-box-containing transcription factors. It is expressed in the developing somites, dorsal spinal cord, mesencephalon and neural crest derivatives. Several loss-of-function mutations are correlated with the Splotch phenotype in mice and Waardenburg syndrome in humans. Malformations include a lack of muscle in the limb, a failure of neural tube closure and dysgenesis of numerous neural crest derivatives. In this study we have used embryonic stem (ES) cells to generate a lacZ knock-in into the Pax3 locus. The Pax3 knock-in Splotch allele (Sp2G) was used to generate Pax3-deficient ES cells in order to investigate whether, in chimeric embryos, Pax3 is acting cell autonomously in the somites and the neural tube. We found that while Pax3 function is essential for the neuroepithelium and somites, a wild-type environment rescues mutant neural crest cells. In the two affected embryonic tissues, mutant and wild-type cells undergo segregation and do not intermingle.The contribution of mutant cells to the neural tube and the somites displayed temporal differences. All chimeric embryos showed a remarkable contribution of blue cells to the neural tube at all stages analyzed, indicating that the Pax3-deficient cells are not excluded from the neural epithelium while development proceeds. In contrast, this is not true for the paraxial mesoderm. The somite contribution of Pax3−/− ES cells becomes less frequent in older embryos as compared to controls with Pax3+/− ES cells. We propose that although Pax3 function is related to cell surface properties, its role may differ in various tissues. In fact, apoptosis was found in Pax3-deficient cells of the lateral dermomyotome but not in the neural tube.

A high level of KLF12 causes folic acid-resistant neural tube defects by activating the Shh signalling pathway in mice

2021 ◽  
Author(s):  
Yang Liu ◽  
Qiong Yuan ◽  
Zhilong Wang ◽  
Lijun Ding ◽  
Na Kong ◽  
...  
Keyword(s):  
Folic Acid ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Signalling Pathway ◽  
Neural Tube Closure ◽  
Health Concern ◽  
Global Public Health ◽  
Interacting Protein ◽  
Patched 1 ◽  
High Level

Abstract Although adequate periconceptional folic acid (FA) supplementation has reduced the occurrence of pregnancies affected by neural tube defects (NTDs), the mechanisms underlying FA-resistant NTDs are poorly understood, and thus NTDs still remain a global public health concern. A high level of Krüppel-like factor 12 (KLF12) exerts deleterious effects on heath in most cases, but evidence for its roles in development has not been published. We observed KLF12-overexpressing mice showed disturbed neural tube development. KLF12-overexpressing foetuses died in utero at approximately 10.5 days post coitus, with 100% presenting cranial NTDs. Neither FA nor formate promoted normal neural tube closure in mutant foetuses. The RNA-seq results showed that a high level of KLF12 caused NTDs in mice via overactivating the sonic hedgehog (Shh) signalling pathway, leading to the upregulation of patched 1, GLI-Krüppel family member GLI1, hedgehog-interacting protein, etc., while FA metabolism-related enzymes did not express differently. PF-5274857, an antagonist of the Shh signalling pathway, significantly promoted dorsolateral hinge point formation and partially rescued the NTDs. The regulatory hierarchy between a high level of KLF12 and FA-resistant NTDs might provide new insights into the diagnosis and treatment of unexplained NTDs in the future.

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.

Development and characterization of commissural interneurones in the spinal cord of Xenopus laevis embryos revealed by antibodies to glycine

Development ◽  
1988 ◽  
Vol 103 (3) ◽  
pp. 447-461 ◽  
Author(s):  
A. Roberts ◽  
N. Dale ◽  
O.P. Ottersen ◽  
J. Storm-Mathisen
Keyword(s):  
Spinal Cord ◽  
Xenopus Laevis ◽  
Neural Tube ◽  
Detailed Comparison ◽  
Neural Tube Closure ◽  
Spinal Interneurones ◽  
Inhibitory Function ◽  
Process Formation ◽  
Xenopus Laevis Embryos

By using an antibody to glutaraldehyde fixation products of glycine we have been able to observe the development of a defined population of spinal interneurones in the CNS of Xenopus laevis embryos. The first glycine immunoreactive (GLY) somata appeared at stage 22 in the caudal hindbrain within a few hours of neural tube closure. The population then increased by extending caudally into the spinal cord and by infill. It was followed up to the time of hatching, stage 37/38. By observing GLY cells at early stages in their differentiation, the normal sequence of cell process formation was deduced. A ventral axon is formed, extends dendrites laterally into the marginal zone and forms a commissure by growing through the ventral ependymal cell floor of the neural tube. On the opposite side, growth cones turn longitudinally and TEM observations show that they make en-passant synaptic contacts. All GLY cells have decussating axons and some grow secondary axons on the same side as the soma. To establish the identity of GLY cells, a detailed comparison was made with commissural and dorsolateral commissural interneurones defined by retrograde and intracellular HRP staining. The GLY cells are identified with the commissural interneurones which are known to serve a glycinergic reciprocal inhibitory function. By showing that these interneurones have a clearly defined group identity and programme of development, this study opens the way to further experiments on factors controlling spinal cord pathway determination.

A critical period for the specification of motor pools in the chick lumbosacral spinal cord

Development ◽  
1996 ◽  
Vol 122 (2) ◽  
pp. 659-669 ◽  
Author(s):  
M.P. Matise ◽  
C. Lance-Jones
Keyword(s):  
Spinal Cord ◽  
Neural Tube ◽  
Regional Differences ◽  
Critical Period ◽  
Local Environment ◽  
Lumbosacral Spinal Cord ◽  
Motor Columns ◽  
Anterior Posterior ◽  
Anterior Posterior Axis

When 3–4 segments of the chick lumbosacral neural tube are reversed in the anterior-posterior axis at stage 15 (embryonic day 2.5), the spinal cord develops with a reversed organization of motoneurons projecting to individual muscles in the limb (C. Lance-Jones and L. Landmesser (1980) J. Physiol. 302, 581–602). This finding indicated that motoneuron precursors or components of their local environment were specified with respect to target by stage 15. To identify the timing of this event, we have now assessed motoneuron projections after equivalent neural tube reversals at earlier stages of development. Lumbosacral neural tube segments 1–3 (+/− one segment cranial or caudal) were reversed in the anterior-posterior axis at stages 13 and 14 (embryonic day 2). The locations of motoneurons innervating two thigh muscles, the sartorius and femorotibialis, were mapped via retrograde horseradish peroxidase labeling at stages 35–36 (embryonic days 9–10). In a sample of embryos, counts were made of the total number of motoneurons in the lateral motor columns of reversed segments. The majority of motoneurons projecting to the sartorius and femorotibialis were in a normal position within the spinal cord. Segmental differences in motor column size were also similar to normal. These observations indicate that positional cues external to the LS neural tube can affect motoneuron commitment and number at stages 13–14. Since these observations stand in contrast to results following stage 15 reversals, we conclude that regional differences related to motoneuron target identity are normally specified or stabilized within the anterior LS neural tube between stages 14 and 15. To examine the role of the notochord in this process, neural tube reversals were performed at stages 13–14 as described above, except that the underlying notochord was also reversed. Projections to the sartorius and femorotibialis muscles did not differ significantly from those in embryos with neural tube reversals alone, indicating that the notochord is not the source of cues for target identity at stages 13–14.

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.

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 .

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