scholarly journals Proliferation-independent regulation of organ size by Fgf/Notch signaling

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Agnė Kozlovskaja-Gumbrienė ◽  
Ren Yi ◽  
Richard Alexander ◽  
Andy Aman ◽  
Ryan Jiskra ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Adhesion ◽  
Notch Signaling ◽  
Hippo Pathway ◽  
Organ Size ◽  
Junctional Complex ◽  
Lateral Line System ◽  
Fgf Signaling ◽  
Line System ◽  
Apical Junctional Complex

Organ morphogenesis depends on the precise orchestration of cell migration, cell shape changes and cell adhesion. We demonstrate that Notch signaling is an integral part of the Wnt and Fgf signaling feedback loop coordinating cell migration and the self-organization of rosette-shaped sensory organs in the zebrafish lateral line system. We show that Notch signaling acts downstream of Fgf signaling to not only inhibit hair cell differentiation but also to induce and maintain stable epithelial rosettes. Ectopic Notch expression causes a significant increase in organ size independently of proliferation and the Hippo pathway. Transplantation and RNASeq analyses revealed that Notch signaling induces apical junctional complex genes that regulate cell adhesion and apical constriction. Our analysis also demonstrates that in the absence of patterning cues normally provided by a Wnt/Fgf signaling system, rosettes still self-organize in the presence of Notch signaling.

Development of the lateral line system in Xenopus laevis

Development ◽  
1985 ◽  
Vol 88 (1) ◽  
pp. 183-192
Author(s):  
Rudolf Winklbauer ◽  
Peter Hausen
Keyword(s):  
Cell Size ◽  
Frequency Distribution ◽  
Lateral Line ◽  
Cell Mass ◽  
Cell Number ◽  
Organ Size ◽  
Cell Counting ◽  
Lateral Line System ◽  
Final Size ◽  
Line System

During normal development of the supraorbital lateral line system of Xenopus, an elongated streak of primordial cells becomes subdivided into a linear series of cell groups containing only about eight cells each, thus forming a row of primary lateral line organs (Winklbauer & Hausen, 1983a,b). In triploid Xenopus embryos, cell size is 1·5 × normal. When the formation of lateral line organs occurs in triploid primordia, the nascent organs contain only about five or six cells each, i.e. about two thirds of normal. Thus, the increase in cell size is compensated for by a corresponding reduction in cell number, keeping constant the organ size in terms of total cell mass or volume. This result excludes a cell counting mechanism for determining organ size. In diploids, the primary organs, although being of equal size initially, differ vastly in their final size and exhibit a peculiar frequency distribution of organ sizes. A detailed quantitative model for supraorbital lateral line development has been proposed, which accounts for this characteristic frequency distribution (Winklbauer & Hausen, 1983b). This model makes precise predictions as to the frequency distribution of the final size of triploid lateral line organs, where the initial organ size is reduced to five or six cells. These predictions were verified experimentally.

scholarly journals Quantitative proximity proteomics resolves the epithelial apical-lateral border and uncovers a vertebrate marginal zone defined by the polarity protein Pals1

2019 ◽  
Author(s):  
Benedict Tan ◽  
Suat Peng ◽  
Sara Sandin ◽  
Jayantha Gunaratne ◽  
Walter Hunziker ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Marginal Zone ◽  
Hippo Pathway ◽  
Molecular Organization ◽  
Junctional Complex ◽  
Lateral Border ◽  
Spatially Resolved ◽  
Apical Junctional Complex ◽  
Membrane Compartment ◽  
Associated Proteins

AbstractEpithelial apico-basal polarity is established through the asymmetric cortical distribution of the Par, Crumbs and Scribble polarity modules. Apical (Par and Crumbs) and basolateral (Scribble) polarity modules overlap at the apical-lateral border, which, in mammals, is defined by the apical junctional complex (AJC). The AJC is composed of tight junctions (TJ) and adherens junctions (AJ) and plays fundamental roles in epithelial morphogenesis and plasticity. However, the molecular composition and precise sub-junctional organization of the AJC and its associated polarity regulators are still not well defined. Here we used the peroxidase APEX2 for quantitative proximity proteomics (QPP) and electron microscopy (EM) imaging to generate a nanometer-scale spatio-molecular map of the apical-lateral border in fully polarized MDCK-II cells. Using Par3 and Pals1 as surrogates for QPP we present a spatially resolved network of ∼800 junction-associated proteins. The network dissects TJ and AJ components and provides strong evidence that TJ are composed of distinct apical and basal subdomains. Moreover, we find that Pals1 and its binding partners PatJ, Lin7c and Crumbs3 define a hitherto unidentified membrane compartment apical of TJ, which we coin the vertebrate marginal zone (VMZ). The VMZ is physically associated with HOMER scaffolding proteins, regulators of apical exocytosis, and membrane-proximal HIPPO pathway proteins. Taken together our work defines the spatial and molecular organization of the apical-lateral border in fully polarized mammalian epithelial cells, reveals an intriguing molecular and spatial conservation of invertebrate and vertebrate cell polarity protein domains, and provides a comprehensive resource of potentially novel regulators of cell polarity and the mammalian AJC.

scholarly journals Histone Demethylase PHF8 Is Required for the Development of the Zebrafish Inner Ear and Posterior Lateral Line

2020 ◽  
Vol 8 ◽  
Author(s):  
Jing He ◽  
Zhiwei Zheng ◽  
Xianyang Luo ◽  
Yongjun Hong ◽  
Wenling Su ◽  
...  
Keyword(s):  
Cell Migration ◽  
Inner Ear ◽  
Lateral Line ◽  
Target Genes ◽  
Histone Demethylase ◽  
Otic Vesicle ◽  
Lateral Line System ◽  
Potential Candidate ◽  
Line System ◽  
Posterior Lateral Line

Histone demethylase PHF8 is crucial for multiple developmental processes, and hence, the awareness of its function in developing auditory organs needs to be increased. Using in situ hybridization (ISH) labeling, the mRNA expression of PHF8 in the zebrafish lateral line system and otic vesicle was monitored. The knockdown of PHF8 by morpholino significantly disrupted the development of the posterior lateral line system, which impacted cell migration and decreased the number of lateral line neuromasts. The knockdown of PHF8 also resulted in severe malformation of the semicircular canal and otoliths in terms of size, quantity, and position during the inner ear development. The loss of function of PHF8 also induced a defective differentiation in sensory hair cells in both lateral line neuromasts and the inner ear. ISH analysis of embryos that lacked PHF8 showed alterations in the expression of many target genes of several signaling pathways concerning cell migration and deposition, including the Wnt and FGF pathways. In summary, the current findings established PHF8 as a novel epigenetic element in developing auditory organs, rendering it a potential candidate for hearing loss therapy.

Angiomotin to regulate prostate cancer cell proliferation by signaling through Hippo-YAP pathway.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e559-e559
Author(s):  
Pengfei Shen ◽  
Hao Zeng ◽  
Angelica Ortiz ◽  
Chien-Jui Cheng ◽  
Yu-Chen Lee ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Nuclear Translocation ◽  
Hippo Pathway ◽  
Neurofibromatosis Type ◽  
Tumor Promoter ◽  
Migration And Invasion ◽  
Junctional Complex ◽  
Chi Square ◽  
Apical Junctional Complex

e559 Background: Angiomotin (AMOT) is a family of proteins found to be a component of the apical junctional complex of vertebrate epithelial cells and is recently found to play important roles in neurofibromatosis type 2 (NF-2). Whether AMOT plays a role in prostate cancer (PCa) is unknown. Methods: Purified GST-AMOTp80 was used as immunogen for antibody generation. Real-time PCR, western blot and immunohistochemistry were used to identify the expression of AMOT. To study the function of AMOT, retroviral vector were constructed, also shRNA was used to knockdown AMOT in cells. Cell migration and invasion assays were performed by using transwell chambers. Nuclear and cytoplasmic protein fractions were prepared by using NE-PER reagents (Pierce). The SPSS 19.0 software was used for statistical analysis. Chi-square test and t test were used for the comparisons between groups. Results: AMOT is expressed as two isoforms, AMOTp80 and AMOTp130, which has a 409 aa N-terminal domain that is absent in AMOTp80. Both AMOTp80 and AMOTp130 are expressed in LNCaP and C4-2B4, but at a low to undetectable level in PC3 cells. Further study showed that AMOTp130 and AMOTp80 have distinct functions in PCa cells. We found that AMOTp80 functioned as a tumor promoter by enhancing PCa cell proliferation while AMOTp130 did not. Mechanistic studies showed that AMOTp80 signaled through the Hippo pathway by promoting the nuclear translocation of YAP, resulting in an increased expression of YAP target protein BMP4. Moreover, inhibition of BMP receptor activity by LDN-193189 abrogates AMOTp80-mediated cell proliferation. Conclusions: Together, this study reveals a novel mechanism whereby the AMOTp80-Merlin-MST1-LATS-YAP-BMP4 pathway leads to AMOTp80-induced tumor cell proliferation.

Development of the lateral line system in Xenopus laevis

Development ◽  
1985 ◽  
Vol 88 (1) ◽  
pp. 193-207
Author(s):  
Rudolf Winklbauer ◽  
Peter Hausen
Keyword(s):  
Lateral Line ◽  
Normal Development ◽  
Organ Size ◽  
Periodic Pattern ◽  
Lateral Line System ◽  
Line System ◽  
Forming Mechanism ◽  
Normal Number ◽  
Cell Groups ◽  
Pattern Forming

The periodic pattern of the supraorbital lateral line organs forms in the epidermis of Xenopus by the subdivision of a streak-like primordium into a linear series of small cell groups. In normal development, each such organ initially contains about 8 cells (Winklbauer & Hausen, 1983a, b). To see whether this initial organ size depends on the size of the streak-like primordium at the time of organ segregation, primordium size was reduced experimentally before the onset of pattern formation. In such small primordia, the size of the primary organs formed is not adjusted so as to allow the formation of a normal number of organs. Instead, the initial organ size is kept approximately normal, and the number of organs is correspondingly reduced, i.e. the pattern forming mechanism is not capable of ‘size regulation’.

scholarly journals The multifarious regulation of the apical junctional complex

Open Biology ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 190278 ◽  
Author(s):  
Alexandra D. Rusu ◽  
Marios Georgiou
Keyword(s):  
Cell Adhesion ◽  
Cell Junctions ◽  
Junctional Complex ◽  
Tissue Architecture ◽  
Comprehensive Overview ◽  
Cell Behaviour ◽  
Apical Junctional Complex ◽  
Mediate Cell ◽  
And Function ◽  
Cell Cell

Epithelial cells form highly organized polarized sheets with characteristic cell morphologies and tissue architecture. Cell–cell adhesion and intercellular communication are prerequisites of such cohesive sheets of cells, and cell connectivity is mediated through several junctional assemblies, namely desmosomes, adherens, tight and gap junctions. These cell–cell junctions form signalling hubs that not only mediate cell–cell adhesion but impact on multiple aspects of cell behaviour, helping to coordinate epithelial cell shape, polarity and function. This review will focus on the tight and adherens junctions, constituents of the apical junctional complex, and aims to provide a comprehensive overview of the complex signalling that underlies junction assembly, integrity and plasticity.

scholarly journals Shootins mediate collective cell migration and organogenesis of the zebrafish posterior lateral line system

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Akihiro Urasaki ◽  
Seiya Morishita ◽  
Kosuke Naka ◽  
Minato Uozumi ◽  
Kouki Abe ◽  
...  
Keyword(s):  
Cell Migration ◽  
Lateral Line ◽  
Lateral Line System ◽  
Collective Cell Migration ◽  
Line System ◽  
Posterior Lateral Line

scholarly journals ZO-2 Is a Master Regulator of Gene Expression, Cell Proliferation, Cytoarchitecture, and Cell Size

2019 ◽  
Vol 20 (17) ◽  
pp. 4128 ◽  
Author(s):  
Lorenza González-Mariscal ◽  
Helios Gallego-Gutiérrez ◽  
Laura González-González ◽  
Christian Hernández-Guzmán
Keyword(s):  
Cell Proliferation ◽  
Cultured Cells ◽  
Hippo Pathway ◽  
Junctional Complex ◽  
Rho Proteins ◽  
Downstream Signaling ◽  
Calcium Sensing ◽  
Apical Junctional Complex ◽  
Regulator Protein ◽  
The Hippo Pathway

ZO-2 is a cytoplasmic protein of tight junctions (TJs). Here, we describe ZO-2 involvement in the formation of the apical junctional complex during early development and in TJ biogenesis in epithelial cultured cells. ZO-2 acts as a scaffold for the polymerization of claudins at TJs and plays a unique role in the blood–testis barrier, as well as at TJs of the human liver and the inner ear. ZO-2 movement between the cytoplasm and nucleus is regulated by nuclear localization and exportation signals and post-translation modifications, while ZO-2 arrival at the cell border is triggered by activation of calcium sensing receptors and corresponding downstream signaling. Depending on its location, ZO-2 associates with junctional proteins and the actomyosin cytoskeleton or a variety of nuclear proteins, playing a role as a transcriptional repressor that leads to inhibition of cell proliferation and transformation. ZO-2 regulates cell architecture through modulation of Rho proteins and its absence induces hypertrophy due to inactivation of the Hippo pathway and activation of mTOR and S6K. The interaction of ZO-2 with viral oncoproteins and kinases and its silencing in diverse carcinomas reinforce the view of ZO-2 as a tumor regulator protein.

Ultrastructure of superficial neuromasts in the mottled sculpin, Cottus bairdi

1989 ◽  
Vol 47 ◽  
pp. 958-959
Author(s):  
W.R. Jones ◽  
S. Coombs ◽  
J. Janssen
Keyword(s):  
Hair Cells ◽  
Lateral Line System ◽  
Electron Microscopic ◽  
Line System ◽  
Dense Cores ◽  
Sensory Hair Cells ◽  
Cytoplasmic Vesicles ◽  
Cottus Bairdi ◽  
Mottled Sculpin ◽  
Upper Third

The lateral line system of the mottled sculpin, like that of most bony fish, has both canal (CNM) and superficial (SNM) sensory end organs, neuromasts, which are distributed on the head and trunk in discrete, readily identifiable groupings (Fig. 1). CNM and SNM differ grossly in location and in overall size and shape. The former are located in subdermal canals and are larger and asymmetric in shape, The latter are located directly on the surface of the skin and are much smaller and more symmetrical It has been suggested that the two may differ at a more fundamental level in such functionally related parameters as extent of myelination of innervating fibers and the absence of efferent innervation in SNM. The present study addresses the validity of these last two features as distinguishing criteria by examining the structure of those SNM populations indicated in Fig. 1 at both the light and electron microscopic levels.All of the populations of SNM examined conform in general to previously published descriptions, consisting of a neuroepithelium composed of sensory hair cells, support cells and mantle cells, Several significant differences from these accounts have, however, emerged. Firstly, the structural composition of the innervating fibers is heterogeneous with respect to the extent of myelination. All SNM groups, with the possible exception of the TRrs and CFLs, possess both myelinated and unmyelinated fibers within the neuroepithelium proper (Fig. 2), just as do CNM. The extent of myelina- tion is quite variable, with some fibers sheath terminating just before crossing the neuroepithelial basal lamina, some just after and a few retaining their myelination all the way to the base of the hair cells in the upper third of the neuroepithelium. Secondly, all SNMs possess fibers that may, on the basis of ultrastructural criteria, be identified as efferent. Such fibers contained numerous cytoplasmic vesicles, both clear and with dense cores. In regions where such fibers closely apposed hair cells, subsynaptic cisternae were observed in the hair cell (Fig. 3).

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