A Novel Role for MAPKAPK2 in Morphogenesis during Zebrafish Development

Holloway, Beth; Canny, Sol Gómez de la Torre; Ye, Ying; Slusarski, Diane C.; Freisinger, Christina M.; Dosch, Roland; Chou, Margaret M.; Wagner, Daniel S.; Mullins, Mary C.

doi:10.1371/journal.pgen.1000413

Cited by 51 publications

(55 citation statements)

References 63 publications

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“…Considering the YCL defects in split top mutants, it is possible that Ctsba itself functions exclusively within the yolk cell, as we found for the maternal-effect mutant betty boop (also known as mapkapk2a) (Holloway et al, 2009). To test whether Ctsba functions solely in the yolk cell, we injected split top embryos with ctsba mRNA either at the one-cell stage or in the yolk at a mid-blastula stage (high to dome stage).…”

Section: Molecular Nature Of the Split Top Genementioning

confidence: 67%

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: Molecular Nature Of the Split Top Genementioning

confidence: 67%

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

et al. 2016

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“…Epiboly in zebrafish, which we will discuss further in Sect. 5, represents the first coordinated cell movement of gastrulation, starting just after blastula stage of the embryo between 4 and 14 hpf (Warga and Kimmel 1990) and is regulated by MAPK (Holloway et al 2009). …”

Section: The Genetic Regulatory Network Controlling Wingless Signallimentioning

confidence: 99%

“…Calcium waves have been described to travel through the blastoderm margin during epiboly progression (Köppen et al 2006, Holloway et al 2009); they might play an important role in triggering actomyosin contraction, but further work is needed to clarify this effect.…”

Section: Deep Cells Deep Cellsmentioning

confidence: 99%

Predictive Power of “A Minima” Models in Biology

Almeida

Demongeot

2012

Acta Biotheor

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Many apparently complex mechanisms in biology, especially in embryology and molecular biology, can be explained easily by reasoning at the level of the "efficient cause" of the observed phenomenology: the mechanism can then be explained by a simple geometrical argument or a variational principle, leading to the solution of an optimization problem, for example, via the co-existence of a minimization and a maximization problem (a min-max principle). Passing from a microscopic (or cellular) level (optimal min-max solution of the simple mechanistic system) to the macroscopic level often involves an averaging effect (linked to the repetition of a large number of such microscopic systems with possible random choice of the parameters of each of them) that gives birth to a global functional feature (e.g. at the tissue level). We will illustrate these general principles by building in four different domains of application "a minima" models and showing the main properties of their solutions: (1) extraction of a minimal RNA structure functioning as the first "peptidic machine," a kind of ancestral ribosome; (2) study of a genetic regulatory network of Drosophila centred on Engrailed gene and expressing successively two genes inside a limit cycle; (3) study of a genetic network regulating neural activity and proliferation in mammals; and (4) study of a simple geometric model of epiboly in zebrafish.

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“…This process continues with the thinning and vegetal migration of the blastoderm over the yolk cell until 50% of the yolk surface is covered (50% epiboly) (40)(41)(42), at which time the deep cells begin the second phase of gastrulation involving dorsal convergence and involution movements which form the germ cell layers. Concomitant with this, each of the three cell layers continues to spread over the yolk in the epiboly process until the yolk cell is completely covered and internalized (41)(42)(43)(44). Reducing the levels of cholesterol metabolites in zebrafi sh embryos results in an epiboly-delay phenotype ( 36 ).…”

Section: This Work Was Supported By a Ruth L Kirschtein Predoctoral mentioning

confidence: 99%

Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish

Schwend

Loucks

Snyder

et al. 2011

Journal of Lipid Research

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This article is available online at http://www.jlr.org ( 1,2 ). NP-C symptoms typically appear in childhood, although infant onsets are possible. By the time the disorder's symptoms manifest, signifi cant cellular damage has already occurred. At the cellular level, NP-C is characterized by an aberrant accumulation of unesterifi ed cholesterol and glycolipids in the late endosomes and lysosomes of the endocytotic pathway ( 3-6 ). The disease is caused by mutations in one of two genes, Niemann-Pick disease, type C1 ( NPC1 ), which accounts for 95% of cases, or NiemannPick disease, type C2 ( NPC2 ), which accounts for 4% of cases. The remaining 1% of cases involves patients with confi rmed biochemical defects without an accompanying identifi ed mutation ( 7-10 ).The function of NPC1 involves regulating the movement of LDL-derived cholesterol and plasma-derived glycolipids from the endocytotic pathway to the endoplasmic reticulum/trans-Golgi network (ER/TGN) and the mitochondrial membrane ( 11-15 ). Despite reductions in sterol exit from the endocytotic pathway, NPC1-defi cient cells display normal sterol uptake, proper sterol delivery to the endocytotic organelles, and unperturbed levels of cholesterol ester hydrolysis ( 3,16,17 ). Excessive sterol content in the liver and spleen likely accounts for reports of hepato-splenomegaly, whereas sterol accumulation in the brain may contribute to the neurological deterioration in NP-C patients ( 16,(18)(19)(20).Abstract Niemann-Pick disease, type C (NP-C), often associated with Niemann-Pick disease, type C1 (NPC1) mutations, is a cholesterol-storage disorder characterized by cellular lipid accumulation, neurodegeneration, and reduced steroid production. To study NPC1 function in vivo, we cloned zebrafi sh npc1 and analyzed its gene expression and activity by reducing Npc1 protein with morpholino (MO)-oligonucleotides. Filipin staining in npc1-morphant cells was punctate, suggesting abnormal accumulation of cholesterol. Developmentally, reducing Npc1 did not disrupt early cell fate or survival; however, early morphogenetic movements were delayed, and the actin cytoskeleton network was abnormal. MO-induced defects were rescued with ectopic expression of mouse NPC1 , demonstrating functional gene conservation, and by treatments with steroids pregnenolone or dexamethasone, suggesting that reduced steroidogenesis contributed to abnormal cell movements. Cell death was found in anterior tissues of npc1 morphants at later stages, consistent with fi ndings in mammals. Collectively, these studies show that npc1 is required early for proper cell movement and cholesterol localization and later for cell survival. -Schwend, T., E. J. Loucks, D. Snyder, and S. C. Ahlgren. Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafi sh. J.

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A Novel Role for MAPKAPK2 in Morphogenesis during Zebrafish Development

Cited by 51 publications

References 63 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

Predictive Power of “A Minima” Models in Biology

Requirement of Npc1 and availability of cholesterol for early embryonic cell movements in zebrafish

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