Dissecting the role of Fgf signaling during gastrulation and left-right axis formation in mouse embryos using chemical inhibitors

AbstractOrgan left-right (LR) asymmetry is a conserved vertebrate feature, which is regulated by left-sided activation of Nodal signaling. Nodal asymmetry is established by a leftward fluid-flow generated at the ciliated LR organizer (LRO). While the role of fibroblast growth factor (FGF) signaling pathways during mesoderm development are conserved, diverging results from different model organisms suggested a non-conserved function in LR asymmetry. Here, we demonstrate that FGF is required during gastrulation in a dual function at consecutive stages of Xenopus embryonic development. In the early gastrula, FGF is necessary for LRO precursor induction, acting in parallel to FGF-mediated mesoderm induction. During late gastrulation, the FGF/Ca2+-branch is required for specification of the flow sensing lateral LRO cells, a function related to FGF-mediated mesoderm morphogenesis. This second function in addition requires input from the calcium channel Polycystin-2. Thus, analogous to mesoderm development, FGF activity is required in a dual role for laterality specification, namely for generating and sensing of leftward flow. Moreover, our data show that FGF functions in LR asymmetric development are conserved across vertebrate species, from fish to mammals.

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Localization of Intracisternal a Particle Antigens in Neoplastic Cells and Preimplantation Mouse Embryos

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600003044 ◽

1980 ◽

Vol 38 ◽

pp. 696-697

Author(s):

Thomas T.F. Huang ◽

Patricia G. Calarco

Keyword(s):

Endoplasmic Reticulum ◽

Normal Development ◽

Mouse Embryos ◽

Neoplastic Cells ◽

Large Numbers ◽

Preimplantation Mouse Embryos ◽

Preimplantation Mouse ◽

Intracisternal A Particle ◽

Normal Feature

The stage specific appearance of a retravirus, termed the Intracisternal A particle (IAP) is a normal feature of early preimplantation development. To date, all feral and laboratory strains of Mus musculus and even Asian species such as Mus cervicolor and Mus pahari express the particles during the 2-8 cell stages. IAP form by budding into the endoplasmic reticulum and appear singly or as groups of donut-shaped particles within the cisternae (fig. 1). IAP are also produced in large numbers in several neoplastic cells such as certain plasmacytomas and rhabdomyosarcomas. The role of IAP, either in normal development or in neoplastic behavior, is unknown.

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Centrosome Aurora A gradient ensures single polarity axis in C. elegans embryos

Biochemical Society Transactions ◽

10.1042/bst20200298 ◽

2020 ◽

Vol 48 (3) ◽

pp. 1243-1253 ◽

Cited By ~ 1

Author(s):

Sukriti Kapoor ◽

Sachin Kotak

Keyword(s):

Symmetry Breaking ◽

Cell Fate ◽

Cell Cortex ◽

Axis Formation ◽

Aurora A Kinase ◽

Aurora A ◽

C Elegans ◽

Cell Embryo ◽

Polarity Establishment

Cellular asymmetries are vital for generating cell fate diversity during development and in stem cells. In the newly fertilized Caenorhabditis elegans embryo, centrosomes are responsible for polarity establishment, i.e. anterior–posterior body axis formation. The signal for polarity originates from the centrosomes and is transmitted to the cell cortex, where it disassembles the actomyosin network. This event leads to symmetry breaking and the establishment of distinct domains of evolutionarily conserved PAR proteins. However, the identity of an essential component that localizes to the centrosomes and promotes symmetry breaking was unknown. Recent work has uncovered that the loss of Aurora A kinase (AIR-1 in C. elegans and hereafter referred to as Aurora A) in the one-cell embryo disrupts stereotypical actomyosin-based cortical flows that occur at the time of polarity establishment. This misregulation of actomyosin flow dynamics results in the occurrence of two polarity axes. Notably, the role of Aurora A in ensuring a single polarity axis is independent of its well-established function in centrosome maturation. The mechanism by which Aurora A directs symmetry breaking is likely through direct regulation of Rho-dependent contractility. In this mini-review, we will discuss the unconventional role of Aurora A kinase in polarity establishment in C. elegans embryos and propose a refined model of centrosome-dependent symmetry breaking.

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Role of fibroblast growth factor (FGF) signaling in the neuroendocrine control of human reproduction

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2011.05.042 ◽

2011 ◽

Vol 346 (1-2) ◽

pp. 37-43 ◽

Cited By ~ 15

Author(s):

Hichem Miraoui ◽

Andrew Dwyer ◽

Nelly Pitteloud

Keyword(s):

Growth Factor ◽

Fibroblast Growth Factor ◽

Human Reproduction ◽

Fibroblast Growth ◽

Fgf Signaling ◽

Neuroendocrine Control

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Uncovering the ancestral role of FGF signaling in neural development

Developmental Biology ◽

10.1016/j.ydbio.2011.05.578 ◽

2011 ◽

Vol 356 (1) ◽

pp. 255

Author(s):

Doreen D. Cunningham ◽

Elena S. Casey

Keyword(s):

Neural Development ◽

Fgf Signaling

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Spleen Tyrosine Kinase Inhibition Modulates p53 Activity

Journal of Cell Death ◽

10.1177/1179066017731564 ◽

2017 ◽

Vol 10 ◽

pp. 117906601773156 ◽

Cited By ~ 2

Author(s):

Mohammad Althubiti

Keyword(s):

Tyrosine Kinase ◽

Survival Rates ◽

Lymphocytic Leukemia ◽

Spleen Tyrosine Kinase ◽

Ht1080 Cell ◽

P53 Expression ◽

Chemical Inhibitors ◽

Dependent Mechanism

Spleen tyrosine kinase (SYK) is a cytoplasmic enzyme that promotes survival and proliferation of B cells. SYK inhibition has shown promising results in the treatment of arthritis and chronic lymphocytic leukemia (CLL). However, in other context, it has been shown that SYK overexpression in epithelial cancer cells induced senescence in p53-dependent mechanism, which underscored its antineoplastic activity in vitro. Here, we show that SYK was induced in response of DNA damage in parallel with p53 levels. In addition, using chemical inhibitors of SYK reduced p53 levels in HCT116 and HT1080 cell lines, which underlines the role of SYK inhibition on p53 activity. Furthermore, SYK inhibition modulated the cell growth, which resulted in a decreasing in cell death. Interestingly, SYK expression showed a positive prognosis in patients with solid tumors in correlations with their survival rates, as expected negative correlation was seen between SYK expression and survival rate of patients with CLL. In conclusion, these findings demonstrate that SYK inhibition modulates p53 expression and activity in HCT116 and HT1080 cells. Reconsidering using of SYK inhibitors in clinical setting in the future should be evaluated carefully in accordance with these findings to prevent the formation of secondary malignancies.

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Regulation of Pax-3 expression in the dermomyotome and its role in muscle development

Development ◽

10.1242/dev.120.4.957 ◽

1994 ◽

Vol 120 (4) ◽

pp. 957-971 ◽

Cited By ~ 63

Author(s):

M. Goulding ◽

A. Lumsden ◽

A.J. Paquette

Keyword(s):

Transcription Factors ◽

Muscle Development ◽

Cell Types ◽

Axial Skeleton ◽

Mouse Embryos ◽

Related Gene ◽

Paired Domain ◽

Trunk Musculature ◽

Somitic Mesoderm

The segmented mesoderm in vertebrates gives rise to a variety of cell types in the embryo including the axial skeleton and muscle. A number of transcription factors containing a paired domain (Pax proteins) are expressed in the segmented mesoderm during embryogenesis. These include Pax-3 and a closely related gene, Pax-7, both of which are expressed in the segmental plate and in the dermomyotome. In this paper, we show that signals from the notochord pattern the expression of Pax-3, Pax-7 and Pax-9 in somites and the subsequent differentiation of cell types that arise from the somitic mesoderm. We directly assess the role of the Pax-3 gene in the differentiation of cell types derived from the dermomyotome by analyzing the development of muscle in splotch mouse embryos which lack a functional Pax-3 gene. A population of Pax-3-expressing cells derived from the dermomyotome that normally migrate into the limb are absent in homozygous splotch embryos and, as a result, limb muscles are lost. No abnormalities were detected in the trunk musculature of splotch embryos indicating that Pax-3 is necessary for the development of the limb but not trunk muscle.

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