Myosin Vb Mediated Plasma Membrane Homeostasis Regulates Peridermal Cell Size and Maintains Tissue Homeostasis in the Zebrafish Epidermis

Sonal,; Sidhaye, Jaydeep; Phatak, Mandar; Banerjee, Shamik; Mulay, Aditya; Deshpande, Ojas; Bhide, Sourabh; Jacob, Tressa; Gehring, Ines; Nuesslein-Volhard, Christiane; Sonawane, Mahendra

doi:10.1371/journal.pgen.1004614

Cited by 34 publications

(41 citation statements)

References 82 publications

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“…The reduction in cell number could be caused by decreased EVL cell proliferation or EVL cell loss, with a concomitant expansion of EVL cell size to compensate for the deficiency. Such compensation through EVL cell size alterations has been described previously (Sonal et al, 2014;Xiong et al, 2014). The cause of the reduced EVL cell number might reflect other deficiencies of the EVL, which could also contribute to the morphogenesis defects observed in these mutants.…”

Section: Evl Defectssupporting

confidence: 64%

Split top: A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis

et al. 2016

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The vertebrate embryonic dorsoventral axis is established and patterned by Wnt and bone morphogenetic protein (BMP) signaling pathways, respectively. Whereas Wnt signaling establishes the dorsal side of the embryo and induces the dorsal organizer, a BMP signaling gradient patterns tissues along the dorsoventral axis. Early Wnt signaling is provided maternally, whereas BMP ligand expression in the zebrafish is zygotic, but regulated by maternal factors. Concomitant with BMP activity patterning dorsoventral axial tissues, the embryo also undergoes dramatic morphogenetic processes, including the cell movements of gastrulation, epiboly and dorsal convergence. Although the zygotic regulation of these cell migration processes is increasingly understood, far less is known of the maternal regulators of these processes. Similarly, the maternal regulation of dorsoventral patterning, and in particular the maternal control of ventral tissue specification, is poorly understood. We identified split top, a recessive maternal-effect zebrafish mutant that disrupts embryonic patterning upstream of endogenous BMP signaling. Embryos from split top mutant females exhibit a dorsalized embryonic axis, which can be rescued by BMP misexpression or by derepressing endogenous BMP signaling. In addition to dorsoventral patterning defects, split top mutants display morphogenesis defects that are both BMP dependent and independent. These morphogenesis defects include incomplete dorsal convergence, delayed epiboly progression and an early lysis phenotype during gastrula stages. The latter two morphogenesis defects are associated with disruption of the actin and microtubule cytoskeleton within the yolk cell and defects in the outer enveloping cell layer, which are both known mediators of epiboly movements. Through chromosomal mapping and RNA sequencing analysis, we identified the lysosomal endopeptidase cathepsin Ba (ctsba) as the gene deficient in split top embryos. Our results identify a novel role for Ctsba in morphogenesis and expand our understanding of the maternal regulation of dorsoventral patterning.

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Section: Evl Defectssupporting

confidence: 64%

Split top: A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis

et al. 2016

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“…C). Importantly, the epithelial phenotype has been previously described in a different mutant allele for myo5b (the goosepimples mutant, Sonal et al, ), providing further evidence that our phenotype is caused by disruption to myo5b. myo5b encodes the atypical myosin, MyoVb, which is involved in the trafficking of recycling endosomes back to the plasma membrane.…”

Section: Resultssupporting

confidence: 83%

“…myo5b encodes the atypical myosin, MyoVb, which is involved in the trafficking of recycling endosomes back to the plasma membrane. myo5b is expressed broadly in the embryo at 24 hpf (Sonal et al, ) and restricted to regions consistent with cardiac expression at 42–60 hpf (http://zfin.org). Because the mutation truncates a large portion of the C‐terminus containing functional domains (Fig.…”

Section: Resultsmentioning

confidence: 99%

Myosin Vb is required for correct trafficking of N‐cadherin and cardiac chamber ballooning

Grassini

Silva

Hall

et al. 2019

Developmental Dynamics

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Background During heart morphogenesis, the cardiac chambers undergo ballooning: a process involving regionalized elongation of cardiomyocytes. Cardiomyocyte shape changes require reorganization of the actin cytoskeleton; however, the genetic regulation of this process is not well understood. Results From a forward genetic screen, we identified the zebrafish uq 23ks mutant which manifests chamber ballooning defects. Whole‐genome sequencing‐mapping identified a truncating mutation in the gene, myo5b. myo5b encodes an atypical myosin required for endosome recycling and, consistent with this, increased vesicles were observed in myo5b mutant cardiomyocytes. Expression of RFP‐Rab11a (a recycling endosome marker) confirmed increased recycling endosomes in cardiomyocytes of myo5b mutants. To investigate potential cargo of MyoVb‐associated vesicles, we examined the adherens junction protein, N‐cadherin. N‐cadherin appeared mispatterned at cell junctions, and an increase in the number of intracellular particles was also apparent. Co‐localization with RFP‐Rab11a confirmed increased N‐cadherin‐positive recycling endosomes, demonstrating N‐cadherin trafficking is perturbed in myo5b mutants. Finally, phalloidin staining showed disorganized F‐actin in myo5b cardiomyocytes, suggesting the cytoskeleton fails to remodel, obstructing chamber ballooning. Conclusions MyoVb is required for cardiomyocyte endosomal recycling and appropriate N‐cadherin localization during the onset of chamber ballooning. Cardiomyocytes lacking MyoVb are unable to reorganize their actin cytoskeleton, resulting in failed chamber ballooning. Developmental Dynamics 248:284–295, 2019. © 2019 Wiley Periodicals, Inc.

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“…We have recently shown that the gsp locus, which is essential for the maintenance of epidermal architecture, encodes for the actin based molecular motor Myosin Vb (Sonal et al, 2014). While the morphological phenotype in the epidermis subsides after 3dpf, the mutants typically die at the beginning of metamorphosis due to unknown reasons.…”

Section: Resultsmentioning

confidence: 99%

The zebrafish goosepimples/myosin Vb mutant exhibits cellular attributes of human microvillus inclusion disease

Sidhaye

Pinto

Dharap

et al. 2016

Mechanisms of Development

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Microvillus inclusion disease (MVID) is a life-threatening enteropathy characterised by malabsorption and incapacitating fluid loss due to chronic diarrhoea. Histological analysis has revealed that enterocytes in MVID patients exhibit reduction of microvilli, presence of microvillus inclusion bodies and intestinal villus atrophy, whereas genetic linkage analysis has identified mutations in myosin Vb gene as the main cause of MVID. In order to understand the cellular basis of MVID and the associated formation of inclusion bodies, an animal model that develops ex utero and is tractable genetically as well as by microscopy would be highly useful. Here we report that the intestine of the zebrafish goosepimples (gsp)/myosin Vb (myoVb) mutant shows severe reduction in intestinal folds - structures similar to mammalian villi. The loss of folds is further correlated with changes in the shape of enterocytes. In striking similarity with MVID patients, zebrafish gsp/myoVb mutant larvae exhibit microvillus atrophy, microvillus inclusions and accumulation of secretory material in enterocytes. We propose that the zebrafish gsp/myoVb mutant is a valuable model to study the pathophysiology of MVID. Furthermore, owing to the advantages of zebrafish in screening libraries of small molecules, the gsp mutant will be an ideal tool to identify compounds having therapeutic value against MVID.

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Myosin Vb Mediated Plasma Membrane Homeostasis Regulates Peridermal Cell Size and Maintains Tissue Homeostasis in the Zebrafish Epidermis

Cited by 34 publications

References 82 publications

Split top: A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis

Split top: A maternal cathepsin B that regulates dorsoventral patterning and morphogenesis

Myosin Vb is required for correct trafficking of N‐cadherin and cardiac chamber ballooning

The zebrafish goosepimples/myosin Vb mutant exhibits cellular attributes of human microvillus inclusion disease

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