Collagen VI ablation in zebrafish causes neuromuscular defects during developmental and adult stages

Tonelotto, Valentina; Consorti, Chiara; Facchinello, Nicola; Trapani, Valeria; Sabatelli, Patrizia; Giraudo, Chiara; Spizzotin, Marianna; Cescon, Matilde; Bertolucci, Cristiano; Bonaldo, Paolo

doi:10.1016/j.matbio.2022.08.004

Cited by 5 publications

(7 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As fibers in the same muscle can be differentially affected, multiple fibers were analyzed per animal. Results were consistent with other CMD zebrafish mutants [ 21 , 43 , 44 ], showing consistent swelling of the SR with misalignment of adjacent sarcomeres in the most severe cases ( Fig. 7A ).…”

Section: Resultssupporting

confidence: 91%

Removal of pomt1 in zebrafish leads to loss of α-dystroglycan glycosylation and dystroglycanopathy phenotypes

Karas,

Terez,

Mowla

et al. 2024

Human Molecular Genetics

View full text Add to dashboard Cite

Biallelic mutations in Protein O-mannosyltransferase 1 (POMT1) are among the most common causes of a severe group of congenital muscular dystrophies (CMDs) known as dystroglycanopathies. POMT1 is a glycosyltransferase responsible for the attachment of a functional glycan mediating interactions between the transmembrane glycoprotein dystroglycan and its binding partners in the extracellular matrix (ECM). Disruptions in these cell-ECM interactions lead to multiple developmental defects causing brain and eye malformations in addition to CMD. Removing Pomt1 in the mouse leads to early embryonic death due to the essential role of dystroglycan during placental formation in rodents. Here, we characterized and validated a model of pomt1 loss of function in the zebrafish showing that developmental defects found in individuals affected by dystroglycanopathies can be recapitulated in the fish. We also discovered that pomt1 mRNA provided by the mother in the oocyte supports dystroglycan glycosylation during the first few weeks of development. Muscle disease, retinal synapse formation deficits, and axon guidance defects can only be uncovered during the first week post fertilization by generating knock-out embryos from knock-out mothers. Conversely, maternal pomt1 from heterozygous mothers was sufficient to sustain muscle, eye, and brain development only leading to loss of photoreceptor synapses at 30 days post fertilization. Our findings show that it is important to define the contribution of maternal mRNA while developing zebrafish models of dystroglycanopathies and that offspring generated from heterozygous and knock-out mothers can be used to differentiate the role of dystroglycan glycosylation in tissue formation and maintenance.

show abstract

Section: Resultssupporting

confidence: 91%

Removal of pomt1 in zebrafish leads to loss of α-dystroglycan glycosylation and dystroglycanopathy phenotypes

Karas,

Terez,

Mowla

et al. 2024

Human Molecular Genetics

View full text Add to dashboard Cite

show abstract

“…Subsequent studies demonstrated that the occurrence of altered mitochondria in Col6a1 −/− muscle is due to defects in the regulation of the autophagic pathway and that autophagy flux reactivation by pharmacological, genetic, or nutritional approaches is able to rescue the occurrence of dysfunctional organelles, apoptosis, and muscle strength [ 54 , 55 , 56 ]. Interestingly, the same features, namely motility impairment, altered organelle ultrastructure, and defective autophagy were also described in a novel mutant colVI knockout zebrafish, throwing light on the role of colVI during embryonic development and rendering the mentioned features as candidate targets in high-throughput drug screening approaches [ 57 ].…”

Section: Skeletal Musclementioning

confidence: 99%

“…This was paralleled by an increase in the expression of the fetal Chrng and activity-dependent Chrna genes, but not Chrne , indicating NMJ changes and an abnormal neuromuscular transmission, further demonstrated by electrophysiological analysis [ 46 ]. Of note, studies performed on colVI knockout zebrafish demonstrated a reduced motor axon elongation and branching within the myotome at both 24 and 48 h of development, thus revealing an early defect in muscle innervation and, in turn, impairing mutant fish motility [ 57 ].…”

Section: Skeletal Musclementioning

confidence: 99%

“…Of note, articular alterations were reported also in zebrafish in the absence of colVI [ 57 ]. In zebrafish, colVI was found to be highly expressed, starting from 48 h post-fertilization and still detectable at six days post-fertilization at the level of palatoquadrate and ceratohyals cartilages [ 122 ].…”

Section: Cartilagementioning

confidence: 99%

“…When colVI is lacking, the arrangement of ceratohyal angles appear to vary in an age-dependent manner, from narrower angles in the embryos to larger in the adult, in comparison to the wild-type condition. While the presence of an alteration is relevant for clinical considerations, such a contrasting phenotype dependent on the developmental stage is in line with the start of eating behavior that in zebrafish occurs approximately seven days post-fertilization, therefore potentially being an effect of the differential force and functioning exerted by muscles and tendons in the colVI knockout context [ 57 ].…”

Section: Cartilagementioning

confidence: 99%

See 2 more Smart Citations

Collagen VI in the Musculoskeletal System

Martino

Cescon

D’Agostino

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Collagen VI exerts several functions in the tissues in which it is expressed, including mechanical roles, cytoprotective functions with the inhibition of apoptosis and oxidative damage, and the promotion of tumor growth and progression by the regulation of cell differentiation and autophagic mechanisms. Mutations in the genes encoding collagen VI main chains, COL6A1, COL6A2 and COL6A3, are responsible for a spectrum of congenital muscular disorders, namely Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and myosclerosis myopathy (MM), which show a variable combination of muscle wasting and weakness, joint contractures, distal laxity, and respiratory compromise. No effective therapeutic strategy is available so far for these diseases; moreover, the effects of collagen VI mutations on other tissues is poorly investigated. The aim of this review is to outline the role of collagen VI in the musculoskeletal system and to give an update about the tissue-specific functions revealed by studies on animal models and from patients’ derived samples in order to fill the knowledge gap between scientists and the clinicians who daily manage patients affected by collagen VI-related myopathies.

show abstract

Current trends and perspectives on aquatic-derived protein: A focus on structure-technofunctional properties relationship and application for food preservation

Zhou,

Feng,

et al. 2024

Trends in Food Science & Technology

View full text Add to dashboard Cite

Collagen VI ablation in zebrafish causes neuromuscular defects during developmental and adult stages

Cited by 5 publications

References 68 publications

Removal of pomt1 in zebrafish leads to loss of α-dystroglycan glycosylation and dystroglycanopathy phenotypes

Removal of pomt1 in zebrafish leads to loss of α-dystroglycan glycosylation and dystroglycanopathy phenotypes

Collagen VI in the Musculoskeletal System

Current trends and perspectives on aquatic-derived protein: A focus on structure-technofunctional properties relationship and application for food preservation

Contact Info

Product

Resources

About