scholarly journals HoxB genes regulate neuronal delamination in the trunk neural tube by controlling the expression of Lzts1

Development ◽  
2021 ◽  
Vol 148 (4) ◽  
pp. dev195404
Author(s):  
Axelle Wilmerding ◽  
Lucrezia Rinaldi ◽  
Nathalie Caruso ◽  
Laure Lo Re ◽  
Emilie Bonzom ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neural Tube ◽  
Leucine Zipper ◽  
Hox Genes ◽  
Neuronal Diversity ◽  
Loss Of Function ◽  
Mantle Zone ◽  
Hox Proteins ◽  
Additional Function ◽  
Developing Spinal Cord

ABSTRACTDifferential Hox gene expression is central for specification of axial neuronal diversity in the spinal cord. Here, we uncover an additional function of Hox proteins in the developing spinal cord, restricted to B cluster Hox genes. We found that members of the HoxB cluster are expressed in the trunk neural tube of chicken embryo earlier than Hox from the other clusters, with poor antero-posterior axial specificity and with overlapping expression in the intermediate zone (IZ). Gain-of-function experiments of HoxB4, HoxB8 and HoxB9, respectively, representative of anterior, central and posterior HoxB genes, resulted in ectopic progenitor cells in the mantle zone. The search for HoxB8 downstream targets in the early neural tube identified the leucine zipper tumor suppressor 1 gene (Lzts1), the expression of which is also activated by HoxB4 and HoxB9. Gain- and loss-of-function experiments showed that Lzts1, which is expressed endogenously in the IZ, controls neuronal delamination. These data collectively indicate that HoxB genes have a generic function in the developing spinal cord, controlling the expression of Lzts1 and neuronal delamination.

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 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.

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 .

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 Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord

2018 ◽  
Author(s):  
Julien Delile ◽  
Teresa Rayon ◽  
Manuela Melchionda ◽  
Amelia Edwards ◽  
James Briscoe ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Single Cell ◽  
Neural Tube ◽  
Temporal Dynamics ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Neuronal Diversity ◽  
Systematic Analysis ◽  
Neural Tube Development

ABSTRACTThe coordinated spatial and temporal regulation of gene expression in the vertebrate neural tube determines the identity of neural progenitors and the function and physiology of the neurons they generate. Progress has been made deciphering the gene regulatory programmes responsible for this process, however, the complexity of the tissue has hampered the systematic analysis of the network and the underlying mechanisms. To address this, we used single cell mRNA sequencing to profile cervical and thoracic regions of the developing mouse neural tube between embryonic days (e)9.5-e13.5. We confirmed the data accurately recapitulates neural tube development, allowing us to identify new markers for specific progenitor and neuronal populations. In addition, the analysis highlighted a previously underappreciated temporal component to the mechanisms generating neuronal diversity and revealed common features in the sequence of transcriptional events that lead to the differentiation of specific neuronal subtypes. Together the data provide a compendium of gene expression for classifying spinal cord cell types that will support future studies of neural tube development, function, and disease.

scholarly journals Segmental lineage restrictions in the chick embryo spinal cord depend on the adjacent somites

Development ◽  
1991 ◽  
Vol 113 (1) ◽  
pp. 239-244 ◽  
Author(s):  
C.D. Stern ◽  
K.F. Jaques ◽  
T.M. Lim ◽  
S.E. Fraser ◽  
R.J. Keynes
Keyword(s):  
Spinal Cord ◽  
Chick Embryo ◽  
Single Cell ◽  
Neural Tube ◽  
Fluorescent Tracer ◽  
Anteroposterior Axis ◽  
Somite Formation ◽  
Developing Spinal Cord

We have investigated whether the developing spinal cord is intrinsically segmented in its rostrocaudal (anteroposterior) axis by mapping the spread of clones derived from single labelled cells within the neural tube of the chick embryo. A single cell in the ventrolateral neural tube of the trunk was marked in situ with the fluorescent tracer lysinated rhodamine dextran (LRD) and its descendants located after two days of further incubation. We find that clones derived from cells labelled before overt segmentation of the adjacent mesoderm do not respect any boundaries within the neural tube. Those derived from cells marked after mesodermal segmentation, however, never cross an invisible boundary aligned with the middle of each somite, and tend to be elongated along the mediolateral axis of the neural tube. When the somite pattern is surgically disturbed, neighbouring clones derived from neuroectodermal cells labelled after somite formation behave like clones derived from younger cells: they no longer respect any boundaries, and are not elongated mediolaterally. These results indicate that periodic lineage restrictions do exist in the developing spinal cord of the chick embryo, but their maintenance requires the presence of the adjacent somite mesoderm.

scholarly journals Onecut factors and Pou2f2 regulate the distribution of V2 interneurons in the mouse developing spinal cord

2018 ◽  
Author(s):  
Audrey Harris ◽  
Gauhar Masgutova ◽  
Amandine Collin ◽  
Mathilde Toch ◽  
Maria Hidalgo-Figueroa ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Transcription Factors ◽  
Neural Circuits ◽  
B Cell Differentiation ◽  
Loss Of Function ◽  
Neuronal Identity ◽  
Spinal Interneuron ◽  
Embryonic Spinal Cord ◽  
And Migration ◽  
Developing Spinal Cord

AbstractAcquisition of proper neuronal identity and position is critical for the formation of neural circuits. In the embryonic spinal cord, cardinal populations of interneurons diversify into specialized subsets and migrate to defined locations within the spinal parenchyma. However, the factors that control interneuron diversification and migration remain poorly characterized. Here, we show that the Onecut transcription factors are necessary for proper diversification and distribution of the V2 interneurons in the developing spinal cord. Furthermore, we uncover that these proteins restrict and moderate the expression of spinal isoforms of Pou2f2, a transcription factor known to regulate B-cell differentiation. By gain- or loss-of-function experiments, we show that Pou2f2 contribute to regulate the position of V2 populations in the developing spinal cord. Thus, we uncovered a genetic pathway that regulates the diversification and the distribution of V2 interneurons during embryonic development.Significance statementIn this study, we identify the Onecut and Pou2f2 transcription factors as regulators of spinal interneuron diversification and migration, two events that are critical for proper CNS development.

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 .

Impairment Rating and Spinal Cord Injuries: Revisiting the Guides

2010 ◽  
Vol 15 (3) ◽  
pp. 1-7
Author(s):  
Richard T. Katz
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Functional Independence ◽  
Outcome Data ◽  
Multiple Organ ◽  
Loss Of Function ◽  
Sixth Edition ◽  
Organ Systems ◽  
Cord Injury ◽  
Impairment Ratings

Abstract This article addresses some criticisms of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) by comparing previously published outcome data from a group of complete spinal cord injury (SCI) persons with impairment ratings for a corresponding level of injury calculated using the AMA Guides, Sixth Edition. Results of the comparison show that impairment ratings using the sixth edition scale poorly with the level of impairments of activities of daily living (ADL) in SCI patients as assessed by the Functional Independence Measure (FIM) motor scale and the extended FIM motor scale. Because of the combinations of multiple impairments, the AMA Guides potentially overrates the impairment of paraplegics compared with that of quadriplegics. The use and applicability of the Combined Values formula should be further investigated, and complete loss of function of two upper extremities seems consistent with levels of quadriplegia using the SCI model. Some aspects of the AMA Guides contain inconsistencies. The concept of diminishing impairment values is not easily translated between specific losses of function per organ system and “overall” loss of ADLs involving multiple organ systems, and the notion of “catastrophic thresholds” involving multiple organ systems may support the understanding that variations in rating may exist in higher rating cases such as those that involve an SCI.

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