Pathway selection by chick lumbosacral motoneurons during normal development

1981 ◽  
Vol 214 (1194) ◽  
pp. 1-18 ◽  
Keyword(s):  
Cell Death ◽  
Early Stage ◽  
Spinal Nerves ◽  
Functional Connections ◽  
Hindlimb Muscles ◽  
Lateral Motor Column ◽  
Normal Period ◽  
Axon Retraction ◽  
Muscle Nerve ◽  
Specific Muscle

Pathways taken by motoneuron axons from the lumbosacral lateral motor column to individual hindlimb muscles have been characterized throughout the normal period of outgrowth and the establishment of specific functional connections in the chick embryo. Axon pathways from individual cord segments were identified after injections of horseradish peroxidase (HRP) directly into the cord. Labelled motoneuron axons were then traced through the plexus and major nerve trunks to termi­nation sites within the limb. At stages 23-24 labelled axons within spinal nerves have just reached the base of the limb and have begun to converge and form the crural and the ischiadic plexus. Even at this early stage, before periods of muscle cleavage, motoneuron cell death and muscle nerve formation, axons show no evidence of widespread random distribution within the limb. Rather, they generally maintain their anterior-posterior position as far as the base of the limb. At stages 27-30, although axons to individual muscles were found to course in discrete tracts within the plexus and nerve trunks they also changed their topographical position with respect to other axons. Axon pathways to single muscles were characterized by tracing retrogradely labelled axons back to the cord after injections of HRP into specific muscle nerves. Axons destined for a single muscle are intermingled with other axons in the spinal nerves and proximal plexus but by the distal plexus have converged to form a discrete tract which then diverges as an individual muscle nerve at more distal levels. These observations exclude models for the establishment of specific connections in which there is widespread testing of the environment with removal of projection errors by cell death and/or axon retraction. They also exclude models that require axons to maintain their topographical position with respect to each other throughout their course.

Evidence for axonal ‘decision regions’ in the axolotl peripheral nervous system

Development ◽  
1988 ◽  
Vol 102 (4) ◽  
pp. 823-836
Author(s):  
S. Wilson ◽  
N. Holder
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Spatial Organization ◽  
Retrograde Transport ◽  
Branch Points ◽  
Spinal Nerves ◽  
Lateral Motor Column ◽  
Decision Region ◽  
Muscle Nerve ◽  
Axial Musculature

Horseradish peroxidase (HRP) was employed to analyse the spatial organization of axons within nerves of the axolotl peripheral nervous system. HRP applications to the lateral motor column, spinal nerves and muscle nerve branches were examined after orthograde or retrograde transport. Axons change relative positions at particular limb regions, notably at the limb plexi, but also at branch points at other limb levels. Such areas of axon reorganization (termed ‘decision regions’ in line with Tosney & Landmesser (1985) J. Neurosci. 5, 2345) are interspersed by lengths of nerve in which axons run parallel to one another. A decision region is also described which involves only axons destined for axial musculature. The detailed anatomy of axon groups is discussed in terms of the likely mechanisms responsible for its formation during development. We conclude that, despite considerable variation in nerve pattern not seen in higher vertebrates, neuromuscular specificity in the axolotl limb is established largely by local pathway cues guiding axons to their appropriate targets.

The localization of the motoneurons supplying the hindlimb muscles of the mouse

1981 ◽  
Vol 293 (1069) ◽  
pp. 477-508 ◽  
Keyword(s):  
Muscle Mass ◽  
Intramuscular Injection ◽  
Hindlimb Muscles ◽  
Lateral Motor Column ◽  
Spinal Segments ◽  
Muscle Nerve ◽  
Absolute Correlation ◽  
Deep Flexors ◽  
L1 And L2 ◽  
Ventral Muscle

The method of retrograde axonal transport of horseradish peroxidase (HRP) has been used to localize the motoneurons that innervate the mouse hindlimb musculature. Motoneurons were labelled following either intramuscular injection of an HRP solution or application of HRP to the cut end of a muscle nerve. When intramuscular injection was used the nerves to adjacent muscles were cut and deflected from the injection site to prevent motoneurons projecting to these muscles being labelled with HRP. For some muscles this procedure was inadequate since the nerves to adjacent muscles were too short to enable adequate deflexion. The motoneurons projecting to these muscles were labelled by the method of cut nerve exposure. The motoneurons that project to a single muscle or a group of muscles were organized as longitudinal columns. The positions of such motonuclei within the lateral motor column were similar in different animals for any given muscle or muscle group. Motoneurons innervating the anterior and medial femoral muscles were located in spinal segments L1 and L2. Motoneurons innervating the remaining hindlimb muscles were found in segments L3-L5. Topographic relationships between muscle motonuclei were in general found to be similar to those described for the cat. The principal differences to be noted between the two species were that the adductors motonucleus did not overlap with the hamstrings motonucleus in the mouse. Also the motonuclei supplying the deep flexors of the crural musculature and intrinsic musculature of the foot were located more ventrally relative to the posterior crural motonucleus in the mouse as compared to the cat. Consideration of muscle homologies between vertebrate classes enabled comparisons of the localization of motonuclei between the mouse and the other species studied. It was found that topographical relations between motonuclei were similar in all the species so far studied. There was no absolute correlation between the rostrocaudal position of a motonucleus and the position in the hindlimb of the muscle that it innervated. In general, motonuclei innervating muscles derived from the dorsal muscle mass were located lateral to motonuclei innervating muscles derived from the ventral muscle mass. Furthermore, within each muscle mass there is a relationship between rostrocaudal position of a motonucleus and the anteroposterior position of the muscle it supplies. Thus there is a relation between position of a motonucleus within the spinal cord and the derivation from the embryonic muscle mass of the muscle that it supplies.

A study of the development of the head and pharynx of the larval urodele Hynobius and its bearing on the evolution of the vertebrate head

1959 ◽  
Vol 242 (690) ◽  
pp. 151-204 ◽  
Keyword(s):  
Cranial Nerves ◽  
Blood System ◽  
The Other ◽  
Neural Arch ◽  
Classical View ◽  
Spinal Nerves ◽  
Anatomical Features ◽  
Muscle Nerve ◽  
11Th Segment ◽  
Nasal Capsule

The early development of the head and pharynx of Hynobius nebulosus (11.5 to 32 mm long) and retardatus (27 and 37 mm specimens) was investigated in some detail from transverse serial microtome sections. Analysis included the chondrocranium, jaws and hyobranchial skeleton, ossifications, cranial and anterior spinal nerves, musculature, blood system and other associated anatomical features. The structure of the skeletogenous elements in general agreed with earlier descriptions. However, a rudimentary fenestra lateralis nasi is found in the nasal capsule of H. nebulosus , hitherto not reported, and a complete cartilaginous processus pterygoideus, confluent with the trabecula and inner margin of the lamina orbito-nasalis described by Edgeworth (1923 a ), was not extant in any Hynobius specimen. H. retardatus has a hypoglossal foramen (and nerve) and joins H. nebulosus (Fox 1957), Cryptobranchus japonicus and alleghaniensis as the only living Amphibia to possess this structure. The neural arch homology of the occipital crest is reaffirmed. The columella stilus of the 32 mm H. nebulosus is confluent with the pterygo-quadrate cartilage and because the hyoid and columella have a common blastematous origin in Hypogeophis (Marcus 1910), it is suggested that there was an ancestral cartilaginous continuity between the hyoid and pterygo-quadrate cartilage, similar to the commissura terminales of the branchiale. This feature would further emphasize the branchial segmental homologies of the mandibular cartilage, hyoid and branchiale. The pattern of the cranial nerves is similar to that of other urodele larvae and the arrangement of the profundus and maxillaris nerves supports the view of the descent of urodeles from porolepiforme crossopterygians (Jarvik 1942). There is a segmental series of eleven head-pharynx segments, a complete branchial segment including a levator muscle, nerve, cartilage bar and gill cleft. Each post-hyoid segment is complete except for the absence of branchiale V and VI, and behind the fourth functional gill cleft there are three vestigial blind ones and then the larynx and trachea leading to the lungs. The masseter (2nd segment), digastricus (3rd segment), dilator laryngeus (10th segment) and trapezius (11th segment) are considered to be the homologues of the other six intervening levator gill arch muscles. The arytenoid and tracheal cartilages are considered to be branchial bars of the 10th and 11th segments respectively, and the lungs to have developed from gill pouches of the 11th segment which failed to reach the exterior early in vertebrate evolution. The classical view of the homology of the laryngo-tracheal skeleton with a branchial bar enunciated by Gegenbaur and Wilder independently in 1892 is therefore upheld; disagreement is merely a numerical one. The basic segmental components of the amphibian head and pharynx are modified in ontogeny by omission, distortion or addition, in order to fit the animal for a terrestrial existence.

scholarly journals Plasma-borne indicators of inflammasome activity in Parkinson’s disease patients

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Faith L. Anderson ◽  
Katharine M. von Herrmann ◽  
Angeline S. Andrew ◽  
Yuliya I. Kuras ◽  
Alison L. Young ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Nlrp3 Inflammasome ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Inflammasome Activation ◽  
Membrane Pore ◽  
Related Proteins ◽  
Inflammasome Activity

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms and loss of dopaminergic neurons of the substantia nigra. Inflammation and cell death are recognized aspects of PD suggesting that strategies to monitor and modify these processes may improve the management of the disease. Inflammasomes are pro-inflammatory intracellular pattern recognition complexes that couple these processes. The NLRP3 inflammasome responds to sterile triggers to initiate pro-inflammatory processes characterized by maturation of inflammatory cytokines, cytoplasmic membrane pore formation, vesicular shedding, and if unresolved, pyroptotic cell death. Histologic analysis of tissues from PD patients and individuals with nigral cell loss but no diagnosis of PD identified elevated expression of inflammasome-related proteins and activation-related “speck” formation in degenerating mesencephalic tissues compared with controls. Based on previous reports of circulating inflammasome proteins in patients suffering from heritable syndromes caused by hyper-activation of the NLRP3 inflammasome, we evaluated PD patient plasma for evidence of inflammasome activity. Multiple circulating inflammasome proteins were detected almost exclusively in extracellular vesicles indicative of ongoing inflammasome activation and pyroptosis. Analysis of plasma obtained from a multi-center cohort identified elevated plasma-borne NLRP3 associated with PD status. Our findings are consistent with others indicating inflammasome activity in neurodegenerative disorders. Findings suggest mesencephalic inflammasome protein expression as a histopathologic marker of early-stage nigral degeneration and suggest plasma-borne inflammasome-related proteins as a potentially useful class of biomarkers for patient stratification and the detection and monitoring of inflammation in PD.

Motor projection patterns to the hind limb of normal and paralysed chick embryos

Development ◽  
1982 ◽  
Vol 72 (1) ◽  
pp. 269-286
Author(s):  
N. G. Laing
Keyword(s):  
Spinal Cord ◽  
Cell Death ◽  
Hind Limb ◽  
Muscle Volume ◽  
Chick Embryos ◽  
Relative Contribution ◽  
Hind Limbs ◽  
Lateral Motor Column ◽  
Before And After ◽  
Major Period

Counts were made of the number of motoneurons innervating the hind limbs of 10-day normal and paralysed chick embryos whose right hind limb buds had been subjected to varying degrees of amputation prior to innervation. The number of motoneurons on the intact sides of the paralysed embryos was found to be similar to the number present in normal embryos prior to the major period of motoneuron death. Since it has previously been shown that paralysis does not increase the number of motoneurons generated, this means that normal motoneuron death was largely prevented in the paralysed embryos. There were differences in the distributions of motoneurons in the rostrocaudal axis of the spinal cord between normal and paralysed embryos. Therefore, cell death does not eliminate a uniform fraction of motoneurons throughout the rostrocaudal extent of the chick embryo lumbar lateral motor column. It is also argued that there are differences in the relative contribution of the various lumbosacral levels to different parts of the limb, e.g. the shank, before and after the period of cell death. In both normal and paralysed embryos there was a linear relationship between the volume of limb muscle which developed after amputation and the number of motoneurons surviving in the spinal cord. There was no evidence of a ‘compression’ of motoneurons into the remaining muscle either after amputation alone or after amputation combined with paralysis. Motoneurons are therefore rigidly specified for certain parts of the limb. The relationship between motoneuron number and muscle volume on the amputated side differed from that of the intact side. For a similar increase in muscle volume there was a smaller increase in motoneuron number on the intact sides. This suggested a parallel to the paradoxically small increase in motoneuron number that occurs on the addition of a supernumerary limb.

scholarly journals Intracellular amyloid toxicity induces oxytosis/ferroptosis regulated cell death

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Ling Huang ◽  
Daniel B. McClatchy ◽  
Pamela Maher ◽  
Zhibin Liang ◽  
Jolene K. Diedrich ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Model ◽  
Early Stage ◽  
Metabolic Reprogramming ◽  
Therapeutic Interventions ◽  
Amyloid Toxicity ◽  
Cell Death Pathway ◽  
Regulated Cell Death ◽  
Metabolomic Data ◽  
Basic Biology

Abstract Amyloid beta (Aβ) accumulates within neurons in the brains of early stage Alzheimer’s disease (AD) patients. However, the mechanism underlying its toxicity remains unclear. Here, a triple omics approach was used to integrate transcriptomic, proteomic, and metabolomic data collected from a nerve cell model of the toxic intracellular aggregation of Aβ. It was found that intracellular Aβ induces profound changes in the omics landscape of nerve cells that are associated with a pro-inflammatory, metabolic reprogramming that predisposes cells to die via the oxytosis/ferroptosis regulated cell death pathway. Notably, the degenerative process included substantial alterations in glucose metabolism and mitochondrial bioenergetics. Our findings have implications for the understanding of the basic biology of proteotoxicity, aging, and AD as well as for the development of future therapeutic interventions designed to target the oxytosis/ferroptosis regulated cell death pathway in the AD brain.

scholarly journals A Genome-Wide CRISPR Activation Screen Identifies Genes Involved in Protection from Zika Virus Infection

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 149
Author(s):  
Anna Dukhovny ◽  
Kevin Lamkiewicz ◽  
Qian Chen ◽  
Markus Fricke ◽  
Nabila Jabrane-Ferrat ◽  
...  
Keyword(s):  
Cell Death ◽  
Zika Virus ◽  
Early Stage ◽  
Specific Treatment ◽  
Febrile Illness ◽  
Neurological Complications ◽  
Host Factors ◽  
Zikv Infection ◽  
A Genome ◽  
Crispr Activation

Zika virus (ZIKV) is an arthropod-borne emerging pathogen causing febrile illness. ZIKV is associated with the Guillain–Barré syndrome and other neurological complications. The vertical transmission of ZIKV can cause fetus demise, stillbirths or severe congenital abnormalities and neurological complications. There is still no vaccine or specific treatment for ZIKV infection. To identify the host factors that can rescue cells from ZIKV infection, we used a genome-scale CRISPR activation screen. Our highly ranking hits included a short list of interferon-stimulated genes (ISGs) previously reported to have antiviral activity. Validation of the screen results highlighted interferon lambda 2 (IFN-lamda2) and interferon alpha-inducible protein 6 (IFI6) as genes providing high levels of protection from ZIKV infection. The activation of these genes had an effect at an early stage in the viral infection. In addition, infected cells expressing single guide RNAs (sgRNAs) for both of these genes displayed lower levels of cell death than did the controls. Furthermore, the identified genes were significantly induced in ZIKV-infected placenta explants. These results highlighted a set of ISGs directly relevant for rescuing cells from ZIKV infection or its associated cell death, thus substantiating CRISPR activation screens as a valid tool for identifying host factors impeding pathogen infection.

scholarly journals Nep1-like Proteins from Valsa mali Differentially Regulate Pathogen Virulence and Response to Abiotic Stresses

2021 ◽  
Vol 7 (10) ◽  
pp. 830
Author(s):  
Jianying Liu ◽  
Jiajun Nie ◽  
Yali Chang ◽  
Lili Huang
Keyword(s):  
Cell Death ◽  
Early Stage ◽  
Pathogenic Fungus ◽  
Strong Immune Response ◽  
Multiple Sequence ◽  
Cytotoxicity Activity ◽  
Pathogen Virulence ◽  
Apple Leaves ◽  
Its Gene ◽  
Valsa Mali

Necrosis and ethylene-inducing peptide 1(Nep1)-like protein (NLP) is well known for its cytotoxicity and immunogenicity on dicotyledonous, and it has attracted large attention due to its gene expansion and functional diversification in numerous phytopathogens. Here, two NLP family proteins, VmNLP1 and VmNLP2, were identified in the pathogenic fungus Valsa mali. We showed that VmNLP2 but not VmNLP1 induced cell death when transiently expressed in Nicotiana benthamiana. VmNLP2 was also shown to induce cell death in apple leaves via the treatment of the Escherichia coli-produced recombinant protein. VmNLP1 and VmNLP2 transcripts were drastically induced at the early stage of V. mali infection, whereas only VmNLP2 was shown to be essential for pathogen virulence. We also found that VmNLP1 and VmNLP2 are required for maintaining the integrity of cell membranes, and they differentially contribute to V. mali tolerance to salt- and osmo-stresses. Notably, multiple sequence alignment revealed that the second histidine (H) among the conserved heptapeptide (GHRHDWE) of VmNLP2 is mutated to tyrosine (Y). When this tyrosine (Y) was substituted by histidine (H), the variant displayed enhanced cytotoxicity in N. benthamiana, as well as enhanced virulence on apple leaves, suggesting that the virulence role of VmNLP2 probably correlates to its cytotoxicity activity. We further showed that the peptide among VmNLP2, called nlp25 (VmNLP2), triggered strong immune response in Arabidopsis thaliana. This work demonstrates that NLPs from V. mali involve multiple biological roles, and shed new light on how intricately complex the functions of NLP might be.

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