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WIREs Mechanisms of Disease Sep 2021The spinal cord is functionally and anatomically divided into ventrally derived motor circuits and dorsally derived somatosensory circuits. Sensory stimuli originating... (Review)
Review
The spinal cord is functionally and anatomically divided into ventrally derived motor circuits and dorsally derived somatosensory circuits. Sensory stimuli originating either at the periphery of the body, or internally, are relayed to the dorsal spinal cord where they are processed by distinct classes of sensory dorsal interneurons (dIs). dIs convey sensory information, such as pain, heat or itch, either to the brain, and/or to the motor circuits to initiate the appropriate response. They also regulate the intensity of sensory information and are the major target for the opioid analgesics. While the developmental mechanisms directing ventral and dorsal cell fates have been hypothesized to be similar, more recent research has suggested that dI fates are specified by novel mechanisms. In this review, we will discuss the molecular events that specify dorsal neuronal patterning in the spinal cord, thereby generating diverse dI identities. We will then discuss how this molecular understanding has led to the development of robust stem cell methods to derive multiple spinal cell types, including the dIs, and the implication of these studies for treating spinal cord injuries and neurodegenerative diseases. This article is categorized under: Neurological Diseases > Stem Cells and Development.
Topics: Cell Differentiation; Interneurons; Neurons; Spinal Cord; Touch
PubMed: 34730293
DOI: 10.1002/wsbm.1520 -
Mechanisms of Development Jan 1997The idea that chordates, during their evolution, have inverted their dorsoventral body axis has recently gained substantial support. It has been shown that various... (Comparative Study)
Comparative Study Review
The idea that chordates, during their evolution, have inverted their dorsoventral body axis has recently gained substantial support. It has been shown that various dorsoventral patterning genes that are evolutionarily conserved between insects and vertebrates are expressed dorsally in insects, and ventrally in vertebrates, or vice versa. The ventral body side of insects thus seems to correspond to the dorsal body side of vertebrates, and these are nerve cord-bearing, neural body sides in both groups. In order to exclude that the inverted polarity of gene patterning activity is purely accidental, we compare here vertebrate and invertebrate blastula fate maps and their gastrulation patterns in the framework of early gene expression. From this comparison it appears that the neural body sides, 'ventral' in annelids or arthropods, and 'dorsal' in chordates, develop at similar positions with respect to the initial egg asymmetry. In addition, the formation of the neural body sides involves similar movements during gastrulation. We further suggest that the deuterostome gastrulation seen in today's chordates can be derived from a more ancestral gastrulation pattern seen in today's annelids and arthropods, and that the ventral midline cells of insects correspond to the dorsal midline cells of vertebrates.
Topics: Animals; Annelida; Arthropods; Blastocyst; Chordata, Nonvertebrate; Gastrula; Genes, Homeobox
PubMed: 9076674
DOI: 10.1016/s0925-4773(96)00620-x -
Journal of Orthopaedic Surgery and... Apr 2023Bone functional adaptation rationalises the inhomogeneous morphology found in bone. By means of computed tomography osteoabsorptiometry and micro-computed tomography,...
BACKGROUND
Bone functional adaptation rationalises the inhomogeneous morphology found in bone. By means of computed tomography osteoabsorptiometry and micro-computed tomography, the mineralisation of the subchondral endplates and trabecular microstructure of vertebral bodies can be assessed to visualise the chronic loading conditions bone endures over time. In this study, we determined cancellous and compartment-specific trabecular architecture in the cervical vertebra to aid with successful integration of orthopaedic implants.
METHODS
We examined the micro-computed tomography scans of seven prospectively healthy C4 vertebrae, evaluated their microstructure parameters (bone volume fraction (BV/TV), bone surface density (BS/BV), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), trabecular number per volume (Tb.N), connectivity density (Conn.D), structure model index (SMI), and degree of anisotropy (DA), and compared the trabecular architecture in twelve predefined volumes of interest: the cranial and caudal 0-10%, 10-15%, and 25-50% in both the ventral and dorsal half. Using computed tomography osteoabsorptiometry, the subchondral bone mineralisation of the subchondral endplates of nine C4 vertebrae was also evaluated.
RESULTS
Highest mineralisation is located dorsally at the endplates. Tb.Sp and Tb.N were the only two parameters that displayed significant differences in averaged values of VOI. Nonetheless, distinct, consistent ventral-dorsal modulations were seen in matched sample ventral-dorsal comparison in the BV/TV, BS/BV, and SMI overall levels, as well as in Tb.Th in the three caudal levels. To simplify, the vertebra was split into ventral-cranial, dorsal-cranial, ventral-caudal, and dorsal-caudal equal quarters. The ventral quarters display lower BV/TV, respectively, higher BS/BV and SMI than their sample paired dorsal quarters. The ventral-cranial quarter shows the lowest BV/TV and the highest BS/BV and SMI, describing spacious cancellous bone with rod-like trabeculae. In contrast, the dorsal-caudal quarter exhibits the highest BV/TV and Tb.Th and the lowest BS/BV and SMI, illustrating thicker, denser, and more plate-like trabeculae. The dorsal-cranial and ventral-caudal quarters are comparable and represent intermediate characteristics.
CONCLUSIONS
CT-OAM and µCT demonstrate the interdependence of compact and trabecular bone in response to long-term loading conditions. Results show highest mineralisation in the dorso-caudal part of the C4 vertebra. Recommended placement of orthopaedic implants should be positioned dorsally with screws anchored in the dorsal-caudal region.
Topics: X-Ray Microtomography; Bone Density; Skull; Calcification, Physiologic; Cervical Vertebrae
PubMed: 37046305
DOI: 10.1186/s13018-023-03760-2 -
Proceedings. Biological Sciences Feb 2018Butterflies have evolved different colour patterns on their dorsal and ventral wing surfaces to serve different signalling functions, yet the developmental mechanisms...
Butterflies have evolved different colour patterns on their dorsal and ventral wing surfaces to serve different signalling functions, yet the developmental mechanisms controlling surface-specific patterning are still unknown. Here, we mutate both copies of the transcription factor in butterflies using CRISPR/Cas9 and show that expressed dorsally, functions both as a repressor and modifier of ventral wing colour patterns, as well as a promoter of dorsal sexual ornaments in males. We propose that the surface-specific diversification of wing patterns in butterflies proceeded via the co-option of or its downstream effectors into various gene regulatory networks involved in the differentiation of discrete wing traits. Further, interactions between and sex-specific factors such as may have contributed to the origin of sexually dimorphic surface-specific patterns. Finally, we discuss the evolution of eyespot number diversity in the family Nymphalidae within the context of developmental constraints due to regulation.
Topics: Animals; Biological Evolution; Butterflies; Clustered Regularly Interspaced Short Palindromic Repeats; Color; Gene Expression; Gene Regulatory Networks; Insect Proteins; Mutation; Phenotype; Pigmentation; Transcription Factors; Wings, Animal
PubMed: 29467265
DOI: 10.1098/rspb.2017.2685 -
Frontiers in Veterinary Science 2022Traction was used to diagnose instability of a T5-T6 traumatic luxation that was stabilized with locking plates in the laminae and dorsal pedicles. A two-year-old, 27...
Traction was used to diagnose instability of a T5-T6 traumatic luxation that was stabilized with locking plates in the laminae and dorsal pedicles. A two-year-old, 27 kg, female spayed golden retriever was presented to a veterinary teaching hospital after being referred for possible mandibular and spinal fractures after being hit by a car. The dog presented non-ambulatory paraparetic with intact pain perception. Computed tomographic (CT) imaging showed a fifth and sixth thoracic vertebral fracture/luxation, with and without manual traction. Surgical stabilization of the spine was performed with bilateral dorsally placed locking plates (String-of-Pearls, Orthomed, UK) in the laminae and dorsal aspects of the vertebral pedicles. The dog recovered well, and neurologic status improved significantly overnight and continued to improve up until discharge, which was 6 days postoperatively. Upon recheck exam at 8 weeks postoperatively, the dog appeared neurologically normal with no obvious surgical complications. This case demonstrates that diagnostic traction-the process of pulling, during imaging, on the dog's pelvis while the forelimbs are secured in extension-demonstrated instability of the spine which was not readily apparent on initial CT imaging. Additionally, the dorsal locking plate stabilization is a viable fixation option that provided acceptable stabilization of the mid-thoracic vertebrae.
PubMed: 36619957
DOI: 10.3389/fvets.2022.1011983 -
Frontiers in Cell and Developmental... 2022Rnf220 is reported to regulate the patterning of the ventral spinal neural tube in mice. The brainstem has divergent connections with peripheral and central targets and...
Rnf220 is reported to regulate the patterning of the ventral spinal neural tube in mice. The brainstem has divergent connections with peripheral and central targets and contains unique internal neuronal groups, but the role of Rnf220 in the early development of the hindbrain has not been explored. In this study, -Cre-mediated conditional knockout ( CKO) mice were used to examine if is involved in the early morphogenesis of the hindbrain. showed restricted expression in the ventral half of ventricular zone (VZ) of the hindbrain at embryonic day (E) 10.5, and as development progressed, -expressing cells were also present in the mantle zone outside the VZ at E12.5. In CKO embryos, alterations of progenitor domains in the ventral VZ were observed at E10.5. There were significant reductions of the p1 and p2 domains shown by expression of , Olig2, and Nkx6.1, accompanied by a ventral expansion of the Dbx1 p0 domain and a dorsal expansion of the Nkx2.2 p3 domain. Different from the case in the spinal cord, the Olig2 pMN (progenitors of somatic motor neuron) domain shifted and expanded dorsally. Notably, the total range of the ventral VZ and the extent of the dorsal tube were unchanged. In addition, the post-mitotic cells derived from their corresponding progenitor domain, including oligodendrocyte precursor cells (OPCs) and serotonergic neurons (5-HTNs), were also changed in the same trend as the progenitor domains do in the CKO embryos at E12.5. In summary, our data suggest similar functions of Rnf220 in the hindbrain dorsoventral (DV) patterning as in the spinal cord with different effects on the pMN domain. Our work also reveals novel roles of Rnf220 in the development of 5-HTNs and OPCs.
PubMed: 35399523
DOI: 10.3389/fcell.2022.831365 -
The Journal of Hand Surgery Oct 2023The load axis of the carpals is located on the volar side of the normal distal radius. A volar lunate facet fracture (VLFF) is exposed to volar-shearing stress, which...
PURPOSE
The load axis of the carpals is located on the volar side of the normal distal radius. A volar lunate facet fracture (VLFF) is exposed to volar-shearing stress, which can cause volar displacement of the carpus. A previous biomechanical study reported that the load at the scaphoid fossa was located more dorsally and the pressure at the lunate fossa decreased in a dorsally-angulated model. However, the distal radius load distribution for various volar tilts remains unclear. We speculate that if the volar tilt decreases, the load distribution moves dorsally and decreases the stress on the VLFF. Therefore, we analyzed a dorsally-angulated distal radius model to evaluate changes in the load distribution using finite element analysis.
METHODS
A 3-dimensional finite element wrist model was developed using computed tomography images. The ligaments were modeled as tension-only spring elements. We considered the intact wrist model for a volar tilt of 15° and created 5 additional models for volar tilts of 10°, 5°, 0°, -5°, and -10°.
RESULTS
As the dorsal angulation increased, the stress distribution moved from volar to dorsal and from the lunate fossa toward the scaphoid fossa. The maximum stress on the volar lunate facet was reduced as volar tilt decreased. The maximum stress was higher on the lunate fossa for volar tilts from 15° to 5°. In contrast, the maximum stress was higher on the scaphoid fossa for volar tilts of ≤0°.
CONCLUSIONS
Load transmission moved from volar to dorsal and from the lunate fossa to the scaphoid fossa when the volar tilt decreased. Therefore, a decrease in the volar tilt would reduce the load on the VLFF.
CLINICAL RELEVANCE
This study provides surgeons accurate knowledge regarding load distribution of the distal radius for various volar tilts that could be helpful in treating patients with VLFFs.
Topics: Humans; Radius; Finite Element Analysis; Radius Fractures; Wrist Joint; Carpal Bones
PubMed: 35973880
DOI: 10.1016/j.jhsa.2022.02.022 -
BioRxiv : the Preprint Server For... Apr 2024Recent studies in vertebrates and have reshaped models of how the axon guidance cue UNC-6/Netrin functions in dorsal-ventral axon guidance, which was traditionally...
Recent studies in vertebrates and have reshaped models of how the axon guidance cue UNC-6/Netrin functions in dorsal-ventral axon guidance, which was traditionally thought to form a ventral-to-dorsal concentration gradient that was actively sensed by growing axons. In the vertebrate spinal cord, floorplate Netrin1 was shown to be largely dispensable for ventral commissural growth. Rather, short range interactions with Netrin1 on the ventricular zone radial glial stem cells was shown to guide ventral commissural axon growth. In , analysis of dorsally-migrating growth cones during outgrowth has shown that growth cone polarity of filopodial extension is separable from the extent of growth cone protrusion. Growth cones are first polarized by UNC-6/Netrin, and subsequent regulation of protrusion by UNC-6/Netrin is based on this earlier-established polarity (the Polarity/Protrusion model). In both cases, short-range or even haptotactic mechanisms are invoked: in vertebrate spinal cord, interactions of growth cones with radial glia expressing Netrin-1; and in a potential close-range interaction that polarizes the growth cone. To explore potential short-range and long-range functions of UNC-6/Netrin, a potentially membrane-anchored transmembrane UNC-6 (UNC-6(TM)) was generated by genome editing. was hypomorphic for dorsal VD/DD axon pathfinding, indicating that it retained some function. Polarity of VD growth cone filopodial protrusion was initially established in , but was lost as the growth cones migrated away from the source in the ventral nerve cord. In contrast, ventral guidance of the AVM and PVM axons was equally severe in and . Together, these results suggest that retains short-range functions but lacks long-range functions. Finally, ectopic expression from non-ventral sources could rescue dorsal and ventral guidance defects in and . Thus, a ventral directional source of UNC-6 was not required for dorsal-ventral axon guidance, and UNC-6 can act as a permissive, not instructive, cue for dorsal-ventral axon guidance. Possibly, UNC-6 is a permissive signal that activates cell-intrinsic polarity; or UNC-6 acts with another signal that is required in a directional manner. In either case, the role of UNC-6 is to polarize the pro-protrusive activity of UNC-40/DCC in the direction of outgrowth.
PubMed: 38712249
DOI: 10.1101/2024.04.23.590737 -
The Journal of Neuroscience : the... Nov 2013V3 interneurons (INs) are a major group of excitatory commissural interneurons in the spinal cord, and they are essential for producing a stable and robust locomotor...
V3 interneurons (INs) are a major group of excitatory commissural interneurons in the spinal cord, and they are essential for producing a stable and robust locomotor rhythm. V3 INs are generated from the ventral-most progenitor domain, p3, but migrate dorsally and laterally during postmitotic development. At birth, they are located in distinctive clusters in the ventral horn and deep dorsal horn. To assess the heterogeneity of this genetically identified group of spinal INs, we combined patch-clamp recording and anatomical tracing with cluster analysis. We examined electrophysiological and morphological properties of mature V3 INs identified by their expression of tdTomato fluorescent proteins in Sim1(Cre/+); Rosa(floxstop26TdTom) mice. We identified two V3 subpopulations with distinct intrinsic properties and spatial distribution patterns. Ventral V3 INs, primarily located in lamina VIII, possess a few branching processes and were capable of generating rapid tonic firing spikes. By contrast, dorsal V3 INs exhibited a more complex morphology and relatively slow average spike frequency with strong adaptation, and they also displayed large sag voltages and post-inhibitory rebound potentials. Our data suggested that hyperpolarization-activated cation channel currents and T-type calcium channel currents may account for some of the membrane properties of V3 INs. Finally, we observed that ventral and dorsal V3 INs were active in different ways during running and swimming, indicating that ventral V3 INs may act as premotor neurons and dorsal V3 INs as relay neurons mediating sensory inputs. Together, we detected two physiologically and topographically distinct subgroups of V3 INs, each likely playing different roles in locomotor activities.
Topics: Action Potentials; Animals; Animals, Newborn; Basic Helix-Loop-Helix Transcription Factors; Benzimidazoles; Cardiovascular Agents; Cluster Analysis; Cyclopropanes; Electric Stimulation; In Vitro Techniques; Interneurons; Mice; Mice, Transgenic; Motor Activity; Naphthalenes; Nickel; Patch-Clamp Techniques; Proto-Oncogene Proteins c-fos; Pyrimidines; RNA, Untranslated; Repressor Proteins; Spinal Cord; Statistics, Nonparametric
PubMed: 24259577
DOI: 10.1523/JNEUROSCI.2005-13.2013 -
Journal of Orthopaedics Dec 2016Fracture of the distal radius is a common clinical problem. Complex fracture requires open reduction and stabilization with plating to restore anatomy. Dorsal plating...
INTRODUCTION
Fracture of the distal radius is a common clinical problem. Complex fracture requires open reduction and stabilization with plating to restore anatomy. Dorsal plating has advantages of buttressing the fracture better but often complicated with tendon problems as per literature. The rate of complications however, was not compared between the low-profile dorsal and the volar plates.
METHODOLOGY
This was a retrospective study on seventy one patients with dorsally angulated or displaced distal radius fractures, who underwent fixation of fractures with either dorsal or volar locking plate from Jan - Nov 2012. Preoperative radiographs were classified based on Universal and Fernandez classification. Postoperative radiographs were assessed for anatomical restoration of Radial length, radial inclination and volar tilt. Tendon and nerve related complications were assessed and functional evaluation was performed on the basis of PRWE (Patient related wrist evaluation) score.
RESULTS
Both groups were matched for their demographic profile and fracture types (p 0.033). Dorsal plating group had 89% excellent/good restoration and fair in 11%. Volar group had 96% excellent/good restoration and fair in 4%. Statistical analysis was performed with unpaired t test for radiographic parameters. Three patients had tendon related complications in dorsal plating group; two patients in volar group had nerve related complications. Functional outcome with PRWE was comparable between two groups.
CONCLUSION
Results with low profile dorsal plating were comparable to volar plating. Therefore dorsal plating can be used as an alternative method when dorsal buttressing of comminuted fracture is required, especially with concomitant osteoporosis.
PubMed: 27504057
DOI: 10.1016/j.jor.2016.06.017