Suction feeding biomechanics of Polypterus bichir: investigating linkage mechanisms and the contributions of cranial kinesis to oral cavity volume change

Many fishes use substantial cranial kinesis to rapidly increase buccal cavity volume, pulling prey into the mouth via suction feeding. Living polypterids are a key lineage for understanding the evolution and biomechanics of suction feeding due to their phylogenetic position and unique morphology. Polypterus bichir have fewer mobile cranial elements compared to teleosts (e.g., immobile [pre]maxillae) but successfully generate suction through dorsal, ventral, and lateral oral cavity expansion. However, the relative contributions of these motions to suction feeding success have not been quantified. Additionally, extensive body musculature and lack of opercular jaw opening linkages make P. bichir of interest for examining the role of cranial vs. axial muscles in driving mandibular depression. Here we analyze the kinematics of buccal expansion during suction feeding in P. bichir using X-Ray Reconstruction of Moving Morphology (XROMM) and quantify the contributions of skeletal elements to oral cavity volume expansion and prey capture. Mouth gape peaks early in the strike, followed by maximum cleithral and ceratohyal rotations, and finally by opercular and suspensorial abductions, maintaining the anterior-to-posterior movement of water. Using a new method of quantifying bones’ relative contributions to volume change (RCVC) we demonstrate that ceratohyal kinematics are the most significant drivers of oral cavity volume change. All measured cranial bone motions, except abduction of the suspensorium, are correlated with prey motion. Lastly, cleithral retraction is largely concurrent with ceratohyal retraction and jaw depression while the sternohyoideus maintains constant length, suggesting a central role of the axial muscles, cleithrum, and ceratohyal in ventral expansion.

Reemployment of Kupffer's vesicle cells into axial and paraxial mesoderm via transdifferentiation

Kupffer's vesicle (KV) in the teleost embryo is a fluid-filled vesicle surrounded by a layer of epithelial cells with rotating primary cilia. KV transiently acts as the left-right organizer but degenerates after the establishment of left-right asymmetric gene expression. Previous labelling experiments indicated that descendants of KV-epithelial cells are incorporated into mesodermal tissues after KV collapses (KV-collapse) in zebrafish embryos. However, the overall picture of their differentiation potency had been unclear due to the lack of suitable genetic tools and molecular analyses. In the present study, we established a novel zebrafish transgenic line with a promoter of charon, in which all KV-epithelial cells and their descendants are specifically labelled until the larval stage. We found that KV-epithelial cells underwent epithelial-mesenchymal transition upon KV-collapse and infiltrate into adjacent mesodermal progenitors, the presomitic mesoderm and chordoneural hinge. Once incorporated, the descendants of KV-epithelial cells expressed distinct mesodermal differentiation markers and contributed to the mature populations such as the axial muscles and notochordal sheath through normal developmental process. These results indicate that fully differentiated KV-epithelial cells possess unique plasticity in that they are reemployed into mesodermal lineages through transdifferentiation after they complete their initial role in KV.

Progressive Weakness and Rash

A 47-year-old man with hypercholesterolemia sought care for a 4-month history of progressive, proximal upper limb weakness and myalgia, followed by dysphagia, difficulty climbing stairs, and facial rash. Discontinuation of atorvastatin was of no benefit. Neurologic examination showed moderate weakness of the neck flexor muscles, shoulder girdle muscles, and finger extensors, and mild weakness of hip flexor and ankle dorsiflexor muscles. He had a heliotrope rash and Gottron sign. Serum testing showed an increased creatine kinase level. Needle electromyography showed myopathic changes with fibrillation potentials in proximal and axial muscles. Biopsy of the deltoid demonstrated a perifascicular pathologic process, including muscle fiber atrophy, and perivascular inflammatory exudate in the perimysium. Immunocytochemical studies showed patchy loss of intramuscular capillaries, some of which had complement (C5b9) deposition, and sarcoplasmic expression of myxovirus resistance protein A, mainly in the perifascicular regions. Immunologic testing was positive for autoantibodies to nuclear matrix protein 2 and negative for 3-hydroxy-3-methylglutaryl–coenzyme A reductase antibodies. Video swallow studies showed oropharyngeal dysphagia. Pulmonary function tests indicated mildly decreased maximal respiratory pressures but normal diffusing lung capacity for carbon monoxide. The findings were consistent with a diagnosis of dermatomyositis. The patient was started on oral prednisone and azathioprine, after checking for adequate thiopurine methyltransferase activity. Liver function tests and complete blood cell count with differential were assessed to monitor for potential azathioprine toxicity. Intravenous immunoglobulin was given. Follow-up examination revealed mild weakness of the shoulder girdle muscles after immunotherapy, and normal strength and creatine kinase value while on azathioprine monotherapy. Dermatomyositis is an idiopathic inflammatory myopathy. Idiopathic inflammatory myopathy is a group of autoimmune muscle diseases that includes dermatomyositis, polymyositis, inclusion body myositis, immune-mediated necrotizing myopathy, and overlap myositis, including antisynthetase syndrome.

Vestibular Influence on Vertebrate Skeletal Symmetry and Body Shape

Vestibular endorgans in the vertebrate inner ear form the principal sensors for head orientation and motion in space. Following the evolutionary appearance of these organs in pre-vertebrate ancestors, specific sensory epithelial patches, such as the utricle, which is sensitive to linear acceleration and orientation of the head with respect to earth’s gravity, have become particularly important for constant postural stabilization. This influence operates through descending neuronal populations with evolutionarily conserved hindbrain origins that directly and indirectly control spinal motoneurons of axial and limb muscles. During embryogenesis and early post-embryonic periods, bilateral otolith signals contribute to the formation of symmetric skeletal elements through a balanced activation of axial muscles. This role has been validated by removal of otolith signals on one side during a specific developmental period in Xenopus laevis tadpoles. This intervention causes severe scoliotic deformations that remain permanent and extend into adulthood. Accordingly, the functional influence of weight-bearing otoconia, likely on utricular hair cells and resultant afferent discharge, represents a mechanism to ensure a symmetric muscle tonus essential for establishing a normal body shape. Such an impact is presumably occurring within a critical period that is curtailed by the functional completion of central vestibulo-motor circuits and by the modifiability of skeletal elements before ossification of the bones. Thus, bilateral otolith organs and their associated sensitivity to head orientation and linear accelerations are not only indispensable for real time postural stabilization during motion in space but also serve as a guidance for the ontogenetic establishment of a symmetric body.

Influence of different transcranial magnetic stimulation current directions on the corticomotor control of lumbar erector spinae muscles during a static task

Different directions of transcranial magnetic stimulation (TMS) can activate different neuronal circuits. While posteroanterior current (PA-TMS) depolarizes mainly interneurons in primary motor cortex (M1), an anteroposterior current (AP-TMS) has been suggested to activate different M1 circuits and perhaps axons from the premotor regions. Although M1 is also involved in the control of axial muscles, no study has explored if different current directions activate different M1 circuits that may have distinct functional role. The aim of the study was to compare the effect of different current directions (PA- and AP-TMS) on the corticomotor control and spatial cortical organisation of the lumbar erector spinae muscle (LES). Thirthy-four healthy participants were recruited for two independent experiments and LES motor-evoked potentials (MEP) were recorded. In experiment 1 (n=17), active motor threshold (AMT), MEP latencies, recruitment curve (90 to 160% AMT), excitatory and inhibitory intracortical mechanisms using paired-pulse TMS (80% followed by 120% AMT stimuli at 2-3-10 and 15ms inter-stimulus intervals) were tested using a double cone (n=12) and a figure-of-eight (n=5) coils. In experiment 2 (n=17), LES cortical representations were tested using PA- and AP-TMS. AMT was higher for AP- compared to PA-TMS (p=0.002). Longer latencies with AP-TMS were compared to PA-TMS (p=0.017). AP-TMS produced more inhibition compared to PA-TMS at 2ms and 3ms (p=0.010), but no difference was observed for longer intervals. No difference was found for recruitment curve and mapping. Those findings suggest that each PA- and AP-TMS may activate different cortical circuits controlling low back muscles as proposed for hand muscles.

SMN controls neuromuscular junction integrity through U7 snRNP

The neuromuscular junction (NMJ) is an essential synapse for animal survival whose loss is a key hallmark of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). While insights into the function of the causative genes implicate RNA dysregulation in NMJ pathogenesis, the RNA-mediated mechanisms controlling the biology of this specialized synapse that go awry in disease remain elusive. Here, we show that activity of the SMA-determining SMN protein in the assembly of U7 small nuclear ribonucleoprotein (snRNP), which functions in the 3'-end processing of replication-dependent histone mRNAs, is required for NMJ integrity. AAV9-mediated gene delivery of U7-specific Lsm10 and Lsm11 proteins selectively enhances U7 snRNP assembly, corrects histone mRNA processing defects, and rescues key structural and functional abnormalities of neuromuscular pathology in SMA mice - including NMJ denervation, reduced synaptic transmission, and skeletal muscle atrophy. Furthermore, U7 snRNP dysfunction induced by SMN deficiency drives selective loss of the synaptic organizing protein Agrin at NMJs innervating vulnerable axial muscles of SMA mice, revealing an unanticipated link between U7-dependent histone mRNA processing and motor neuron-derived expression of an essential factor for NMJ biology. Together, these findings establish a direct contribution of U7 snRNP dysfunction to the neuromuscular phenotype in SMA and the requirement of RNA-mediated histone gene regulation for maintaining functional synaptic connections between motor neurons and muscles.

Zic1 advances epaxial myotome morphogenesis to cover the neural tube via Wnt11r

The dorsal axial muscles, or epaxial muscles, are a fundamental structure covering the spinal cord and vertebrae, as well as mobilizing the vertebrate trunk. To date, mechanisms underlying the morphogenetic process shaping the epaxial myotome are largely unknown. To address this, we used the medaka zic1/zic4-enhancer mutant Double anal fin (Da), which exhibits ventralized dorsal trunk structures resulting in impaired epaxial myotome morphology and incomplete coverage over the neural tube. In wild type, dorsal dermomyotome (DM) cells, progenitors of myotomal cells, reduce their proliferative activity after somitogenesis and subsequently form unique large protrusions extending dorsally, potentially guiding the epaxial myotome dorsally. In Da, by contrast, DM cells maintain the high proliferative activity and form mainly small protrusions. By combining RNA- and ChIP-sequencing analyses, we revealed direct targets of Zic1 which are specifically expressed in dorsal somites and involved in various aspects of development, such as cell migration, extracellular matrix organization and cell-cell communication. Among these, we identified wnt11r as a crucial factor regulating both cell proliferation and protrusive activity of DM cells. We propose that the dorsal movement of the epaxial myotome is guided by DM cells and that Zic1 empowers this activity via Wnt11r to achieve the neural tube coverage.

Successful treatment with rituximab in a refractory Stiffperson syndrome (SPS)

Background: SPS is a disorder consisting of rigidity of axial muscles with painful spasms. More than 80 % of SPS patients have high titer antibodies against glutamic acid decarboxylase (GAD). The use of rituximab for the treatment of SPS is a recent therapeutical approach showing promising results. We present a case of SPS treated with rituximab, showing a good and safe response. Case: A 38-year-old female patient presented with a history of rigidity of abdominal and paravertebral muscles associated with painful spasms in lower back region, increased tonus, lumbar lordosis, frequent falls and severe functional limitation. The anti-GAD antibodies were positive in high titles. Electromyography showed continuous motor activity with normal morphology especially on paravertebral muscles. She had a partial response to baclofen and diazepam, but could not tolerate it because of somnolence, and started the treatment with rituximab. After one year, the baclofen was discontinued and the diazepam reduced. The axial stiffness and spasm frequency improved, including postural instability, without new episodes of falls. Discussion: Rituximab is a monoclonal antibody targeting the CD20 antigens on the surface of mature B lymphocytes. After binding to these antigens, it initiates a cascade of biochemical events leading to apoptosis. Its use has been approved for numerous diseases with promising results. The use of rituximab in the treatment of SPS is a recent approach and good results have been reported. Conclusion: Rituximab may be a promising option in SPS treatment. However, this is a preliminary paper showing partial results requiring long-term follow-up.

Axial muscle weakness

Axial myopathy is a rare neuromuscular disorder characterised by selective involvement of the paraspinal muscles, and presenting either as a bent spine and/or dropped head syndrome. The axial muscles can be involved in various conditions, including neuromuscular disease, movement disorders, spinal disease and metabolic disorders. There have been recent descriptions of disorders with selective axial muscle involvement, but overall axial myopathy remains under-recognised. Here, we review disorders of axial muscle function, provide guidance on interpreting axial muscles imaging and suggest a diagnostic algorithm to evaluate patients with axial muscles weakness.

Fishes can use axial muscles as anchors or motors for powerful suction feeding

ABSTRACTSome fishes rely on large regions of the dorsal (epaxial) and ventral (hypaxial) body muscles to power suction feeding. Epaxial and hypaxial muscles are known to act as motors, powering rapid mouth expansion by shortening to elevate the neurocranium and retract the pectoral girdle, respectively. However, some species, like catfishes, use little cranial elevation. Are these fishes instead using the epaxial muscles to forcefully anchor the head, and if so, are they limited to lower-power strikes? We used X-ray imaging to measure epaxial and hypaxial length dynamics (fluoromicrometry) and associated skeletal motions (XROMM) during 24 suction feeding strikes from three channel catfish (Ictalurus punctatus). We also estimated the power required for suction feeding from oral pressure and dynamic endocast volume measurements. Cranial elevation relative to the body was small (<5 deg) and the epaxial muscles did not shorten during peak expansion power. In contrast, the hypaxial muscles consistently shortened by 4–8% to rotate the pectoral girdle 6–11 deg relative to the body. Despite only the hypaxial muscles generating power, catfish strikes were similar in power to those of other species, such as largemouth bass (Micropterus salmoides), that use epaxial and hypaxial muscles to power mouth expansion. These results show that the epaxial muscles are not used as motors in catfish, but suggest they position and stabilize the cranium while the hypaxial muscles power mouth expansion ventrally. Thus, axial muscles can serve fundamentally different mechanical roles in generating and controlling cranial motion during suction feeding in fishes.