Microridges are apical projections formed of branched F-actin networks that organize the glycan layer

Cs, Pinto; Khandekar, Ameya; Bhavna, Rajasekaran; Kiesel, Petra; Pigino, Gaia; Sonawane, Mahendra

doi:10.1101/442871

Cited by 8 publications

(9 citation statements)

References 56 publications

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“…We also noticed the association of the WASL gene which act in the cytoskeleton [73], which is a complex network of cells playing a role in muscle contraction. Taken together, due to all mentioned genes above are related with muscle (either connected with muscle structural proteins or muscle development) we hypothesize that the chromosome region on BTA4 (88 Mb spanning about 280 kb), which supports five closely located genes, is a candidate region for skeletal muscle development genes in Simmental beef cattle.…”

Section: Discussionmentioning

confidence: 99%

Identification of muscle-specific candidate genes in Simmental beef cattle using imputed next generation sequencing

et al. 2019

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Genome-wide association studies (GWAS) have commonly been used to identify candidate genes that control economically important traits in livestock. Our objective was to detect potential candidate genes associated mainly with muscle development traits related to dimension of hindquarter in cattle. A next generation sequencing (NGS) dataset to imputed to 12 million single nucleotide polymorphisms (SNPs) (from 1252 Simmental beef cattle) were used to search for genes affecting hindquarter traits using a linear, mixed model approach. We also used haplotype and linkage disequilibrium blocks to further support our identifications. We identified 202 significant SNPs in the bovine BTA4 chromosome region associated with width of hind leg, based on a stringent statistical threshold (p = 0.05/ effective number of SNPs identified). After exploring the region around these SNPs, we found candidate genes that were potentially related to the associated markers. More importantly, we identified a region of approximately 280 Kb on the BTA4 chromosome that harbored several muscle specific candidate genes, genes to be in a potential region for muscle development. However, we also found candidate gene SLC13A1 on BTA4, which seems to be associated with bone disorders (such as chondrodysplasia) in Simmental beef cattle.

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Section: Discussionmentioning

confidence: 99%

Identification of muscle-specific candidate genes in Simmental beef cattle using imputed next generation sequencing

et al. 2019

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“…Three classes of actin nucleators have been described previously in zebrafish, Arp2/3 complex, Formin homology domain 2 (FH2) containing family (the Formins) and the WASP homology domain 2 (WH2) containing family of nucleators. Arp2/3 has been shown to regulate actin patches essential for proximal axon specification in zebrafish motor neurons (Balasanyan et al, 2017) and maintenance of microridge structure and length on surface epithelial cells in zebrafish (Lam et al, 2015;Pinto et al, 2019). The WH2 domain containing actin nucleator, Cordon bleu (Cobl), is required for the development of motile cilia in zebrafish Kuppfer's vesicles which in turn maintain laterality in zebrafish (Ravanelli and Klingensmith, 2011).…”

Section: Discussionmentioning

confidence: 99%

The formin Fmn2 is required for the development of an excitatory interneuron module in the zebrafish acoustic startle circuit

Nagar

James

Mishra

et al. 2020

Preprint

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The formin family member, Fmn2, is a neuronally enriched cytoskeletal remodelling protein conserved across vertebrates. Recent studies have implicated Fmn2 in neurodevelopmental disorders, including sensory processing dysfunction and intellectual disability in humans. Cellular characterization of Fmn2 in primary neuronal cultures has identified its function in the regulation of cell-substrate adhesion and consequently growth cone translocation. However, the role of Fmn2 in the development of neural circuits in vivo, and its impact on associated behaviours have not been tested.Using automated analysis of behaviour and systematic investigation of the associated circuitry, we uncover the role of Fmn2 in zebrafish neural circuit development. As reported in other vertebrates, the zebrafish ortholog of Fmn2 is also enriched in the developing zebrafish nervous system. We find that Fmn2 is required for the development of an excitatory interneuron pathway, the spiral fiber neuron, which is an essential circuit component in the regulation of the Mauthner cell-mediated acoustic startle response. Consistent with the loss of the spiral fiber neurons tracts, high-speed video recording revealed a reduction in the short latency escape events while responsiveness to the stimuli was unaffected.Taken together, this study provides evidence for a circuit-specific requirement of Fmn2 in eliciting an essential behaviour in zebrafish. Our findings underscore the importance of Fmn2 in neural development across vertebrate lineages and highlight zebrafish models in understanding neurodevelopmental disorders.SIGNIFICANCE STATEMENTFmn2 is a neuronally enriched cytoskeletal remodelling protein linked to neurodevelopment and cognitive disorders in humans. Recent reports have characterized its function in growth cone motility and chemotaxis in cultured primary neurons. However, the role of Fmn2 in the development of neural circuits in vivo and its implications in associated behaviours remain unexplored. This study shows that Fmn2 is required for the development of neuronal processes in the acoustic startle circuit to ensure robust escape responses to aversive stimuli in zebrafish. Our study underscores the crucial role of the non-diaphanous formin, Fmn2, in establishing neuronal connectivity and related behaviour in zebrafish.

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“…3F). These label-retaining periderm cells, or LRPCs, provided crisp confocal images with well-defined membrane features, including EGFP accumulations in the labyrinthine apical mi-croridges typical of zebrafish epidermis (Bereiter-Hahn et al, 1979;Uehara et al, 1991;Pinto et al, 2018). Scattered LRPCs remained visible, though rarer, up to the mid-pharyngula stage (~30 hpf).…”

Section: Tg(lcp1:cre-p2a-egfp-caax) Embryos Recapitulate Early L-plastin Expressionmentioning

confidence: 99%

Identification of regulatory elements recapitulating early expression of L-plastin in the zebrafish enveloping layer and embryonic periderm

Baumgartner

Compton

Evans

et al. 2019

Gene Expression Patterns

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We have cloned and characterized an intronic fragment of zebrafish lymphocyte cytosolic protein 1 (lcp1, also called L-plastin) that drives expression to the zebrafish enveloping layer (EVL). Lplastin is a calcium-dependent actin-bundling protein belonging to the plastin/fimbrin family of proteins, and is necessary for the proper migration and attachment of several adult cell types, including leukocytes and osteoclasts. However, in zebrafish lcp1 is abundantly expressed much earlier, during differentiation of the EVL. The cells of this epithelial layer migrate collectively, spreading vegetally over the yolk. L-plastin expression persists into the larval periderm, a transient epithelial tissue that forms the first larval skin. This finding establishes that L-plastin is activated in two different embryonic waves, with a distinct regulatory switch between the early EVL and the later leukocyte. To better study L-plastin expressing cells we attempted CRISPR/Cas9 homologydriven recombination (HDR) to insert a self-cleaving peptide (Cre-P2A-EGFP-CAAX) downstream of the native lcp1 promoter. This produced a stable zebrafish line expressing Cre recombinase in EVL nuclei and green fluorescence in EVL cell membranes. In vivo tracking of these labeled cells provided enhanced views of EVL migration behavior, membrane extensions, and mitotic events. Finally, we experimentally dissected key elements of the targeted lcp1 locus, discovering a ~300 bp intronic sequence sufficient to drive EVL expression. The lcp1: Cre-P2A-EGFP-CAAX zebrafish should be useful for studying enveloping layer specification, gastrulation movements and periderm development in this widely used vertebrate model. In addition, the conserved regulatory sequences we have isolated predict that L-plastin orthologs may have a similar early expression pattern in other vertebrate embryos.

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Microridges are apical projections formed of branched F-actin networks that organize the glycan layer

Cited by 8 publications

References 56 publications

Identification of muscle-specific candidate genes in Simmental beef cattle using imputed next generation sequencing

Identification of muscle-specific candidate genes in Simmental beef cattle using imputed next generation sequencing

The formin Fmn2 is required for the development of an excitatory interneuron module in the zebrafish acoustic startle circuit

Identification of regulatory elements recapitulating early expression of L-plastin in the zebrafish enveloping layer and embryonic periderm

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