scholarly journals Natural loss of function of ephrin-B3 shapes spinal flight circuitry in birds

2021 ◽  
Vol 7 (24) ◽  
pp. eabg5968
Author(s):  
Baruch Haimson ◽  
Oren Meir ◽  
Reut Sudakevitz-Merzbach ◽  
Gerard Elberg ◽  
Samantha Friedrich ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mutant Mouse ◽  
Loss Of Function ◽  
Dorsal Midline ◽  
Roof Plate ◽  
Embryonic Spinal Cord ◽  
Guidance Molecule

Flight in birds evolved through patterning of the wings from forelimbs and transition from alternating gait to synchronous flapping. In mammals, the spinal midline guidance molecule ephrin-B3 instructs the wiring that enables limb alternation, and its deletion leads to synchronous hopping gait. Here, we show that the ephrin-B3 protein in birds lacks several motifs present in other vertebrates, diminishing its affinity for the EphA4 receptor. The avian ephrin-B3 gene lacks an enhancer that drives midline expression and is missing in galliforms. The morphology and wiring at brachial levels of the chicken embryonic spinal cord resemble those of ephrin-B3 null mice. Dorsal midline decussation, evident in the mutant mouse, is apparent at the chick brachial level and is prevented by expression of exogenous ephrin-B3 at the roof plate. Our findings support a role for loss of ephrin-B3 function in shaping the avian brachial spinal cord circuitry and facilitating synchronous wing flapping.

scholarly journals Natural loss of function of ephrin-B3 shapes spinal flight circuitry in birds

2021 ◽  
Author(s):  
Baruch Haimson ◽  
Oren Meir ◽  
Reut Sudakevitz-Merzbach ◽  
Gerard Elberg ◽  
Samantha Friedrich ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuronal Network ◽  
Mutant Mouse ◽  
Loss Of Function ◽  
Dorsal Midline ◽  
Roof Plate ◽  
Guidance Molecule ◽  
Chick Spinal Cord

AbstractFlight in birds evolved through patterning of the wings from forelimbs and transition from alternating gait to synchronous flapping. In mammals, the spinal midline guidance molecule ephrin-B3 instructs the wiring that enables limb alternation, and its deletion leads to synchronous hopping gait. Here we show that the ephrin-B3 protein in birds lacks several motifs present in other vertebrates, diminishing its affinity for the EphA4 receptor. The avian ephrin-B3 gene lacks an enhancer that drives midline expression, and is missing in Galliformes. The morphology and wiring at brachial levels of the chick spinal cord resemble those of ephrin-B3 null mice. Importantly, dorsal midline decussation, evident in the mutant mouse, is apparent at the chick brachial level, and is prevented by expression of exogenous ephrin-B3 at the roof plate. Our findings support a role for loss of ephrin-B3 function in shaping the avian brachial spinal cord circuitry and facilitating synchronous wing flapping.TeaserWalking vs flying: Deciphering the organization and evolution of the neuronal network that controls wing flapping in birds.

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.

Oligodendrocyte progenitors in the embryonic spinal cord express DM-20

1996 ◽  
Vol 22 (3) ◽  
pp. 188-198 ◽  
Author(s):  
P. J. Dickinson ◽  
M. L. Fanarraga ◽  
I. R. Griffiths ◽  
J. M. Barrie ◽  
E. Kyriakides ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Oligodendrocyte Progenitors ◽  
Embryonic Spinal Cord

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.

scholarly journals EGCG modulates PKD1 and ferroptosis to promote recovery in ST rats

2020 ◽  
Vol 11 (1) ◽  
pp. 173-181 ◽  
Author(s):  
Jianjun Wang ◽  
Ying Chen ◽  
Long Chen ◽  
Yanzhi Duan ◽  
Xuejun Kuang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Functional Recovery ◽  
Antioxidant Properties ◽  
Underlying Mechanism ◽  
Maximal Effect ◽  
Loss Of Function ◽  
Protein Kinase D1 ◽  
Erk Phosphorylation ◽  
Cord Injury ◽  
Novel Strategy

AbstractBackgroundSpinal cord injury (SCI) causes devastating loss of function and neuronal death without effective treatment. (−)-Epigallocatechin-3-gallate (EGCG) has antioxidant properties and plays an essential role in the nervous system. However, the underlying mechanism by which EGCG promotes neuronal survival and functional recovery in complete spinal cord transection (ST) remains unclear.MethodsIn the present study, we established primary cerebellar granule neurons (CGNs) and a T10 ST rat model to investigate the antioxidant effects of EGCG via its modulation of protein kinase D1 (PKD1) phosphorylation and inhibition of ferroptosis.ResultsWe revealed that EGCG significantly increased the cell survival rate of CGNs and PKD1 phosphorylation levels in comparison to the vehicle control, with a maximal effect observed at 50 µM. EGCG upregulated PKD1 phosphorylation levels and inhibited ferroptosis to reduce the cell death of CGNs under oxidative stress and to promote functional recovery and ERK phosphorylation in rats following complete ST.ConclusionTogether, these results lay the foundation for EGCG as a novel strategy for the treatment of SCI related to PKD1 phosphorylation and ferroptosis.

scholarly journals Knockdown of long non-coding RNA LEF1-AS1 attenuates apoptosis and inflammatory injury of microglia cells following spinal cord injury

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Sheng-Yu Cui ◽  
Wei Zhang ◽  
Zhi-Ming Cui ◽  
Hong Yi ◽  
Da-Wei Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Viability ◽  
Microglial Cells ◽  
Protective Effects ◽  
Loss Of Function ◽  
Sprague Dawley ◽  
Cord Injury ◽  
Apoptosis And Inflammation

Abstract Background Spinal cord injury (SCI) is associated with health burden both at personal and societal levels. Recent assessments on the role of lncRNAs in SCI regulation have matured. Therefore, to comprehensively explore the function of lncRNA LEF1-AS1 in SCI, there is an urgent need to understand its occurrence and development. Methods Using in vitro experiments, we used lipopolysaccharide (LPS) to treat and establish the SCI model primarily on microglial cells. Gain- and loss of function assays of LEF1-AS1 and miR-222-5p were conducted. Cell viability and apoptosis of microglial cells were assessed via CCK8 assay and flow cytometry, respectively. Adult Sprague-Dawley (SD) rats were randomly divided into four groups: Control, SCI, sh-NC, and sh-LEF-AS1 groups. ELISA test was used to determine the expression of TNF-α and IL-6, whereas the protein level of apoptotic-related markers (Bcl-2, Bax, and cleaved caspase-3) was assessed using Western blot technique. Results We revealed that LncRNA LEF1-AS1 was distinctly upregulated, whereas miR-222-5p was significantly downregulated in LPS-treated SCI and microglial cells. However, LEF1-AS1 knockdown enhanced cell viability, inhibited apoptosis, as well as inflammation of LPS-mediated microglial cells. On the contrary, miR-222-5p upregulation decreased cell viability, promoted apoptosis, and inflammation of microglial cells. Mechanistically, LEF1-AS1 served as a competitive endogenous RNA (ceRNA) by sponging miR-222-5p, targeting RAMP3. RAMP3 overexpression attenuated LEF1-AS1-mediated protective effects on LPS-mediated microglial cells from apoptosis and inflammation. Conclusion In summary, these findings ascertain that knockdown of LEF1-AS1 impedes SCI progression via the miR-222-5p/RAMP3 axis.

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