scholarly journals A novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusion

2018 ◽  
Author(s):  
Richard W. Naylor ◽  
Alan J. Davidson
Keyword(s):  
Transcription Factor ◽  
Epithelial Cells ◽  
Live Cell Imaging ◽  
Renal Tubule ◽  
Distal Tubule ◽  
Live Cell ◽  
Endocrine Gland ◽  
Apical Constriction ◽  
Naturally Occurring ◽  
Cell Extrusion

AbstractTransdifferentiation is the poorly understood phenomenon whereby a terminally differentiated cell acquires a completely new identity. Here, we describe a rare example of a naturally occurring transdifferentiation in zebrafish in which kidney distal tubule epithelial cells are converted into an endocrine gland known as the Corpuscles of Stannius (CS). We find that this process requires Notch signalling and is associated with the cytoplasmic sequestration of the Hnf1b transcription factor, a master-regulator of renal tubule fate. A deficiency in the Irx3b transcription factor results in ectopic transdifferentiation of distal tubule cells to a CS identity but in a Notch-dependent fashion. Using live-cell imaging we show that CS cells undergo apical constriction en masse and are then extruded from the tubule to form a distinct organ. This system provides a valuable new model to understand the molecular and morphological basis of transdifferentiation and will advance efforts to exploit this rare phenomenon therapeutically.

scholarly journals A novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusion

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Richard W Naylor ◽  
Hao-Han G Chang ◽  
Sarah Qubisi ◽  
Alan J Davidson
Keyword(s):  
Transcription Factor ◽  
Epithelial Cells ◽  
Live Cell Imaging ◽  
Renal Tubule ◽  
Distal Tubule ◽  
Live Cell ◽  
Endocrine Gland ◽  
Apical Constriction ◽  
Naturally Occurring ◽  
Cell Extrusion

Transdifferentiation is the poorly understood phenomenon whereby a terminally differentiated cell acquires a completely new identity. Here, we describe a rare example of a naturally occurring transdifferentiation event in zebrafish in which kidney distal tubule epithelial cells are converted into an endocrine gland known as the Corpuscles of Stannius (CS). We find that this process requires Notch signalling and is associated with the cytoplasmic sequestration of the Hnf1b transcription factor, a master-regulator of renal tubule fate. A deficiency in the Irx3b transcription factor results in ectopic transdifferentiation of distal tubule cells to a CS identity but in a Notch-dependent fashion. Using live-cell imaging we show that CS cells undergo apical constriction en masse and are then extruded from the tubule to form a distinct organ. This system provides a valuable new model to understand the molecular and morphological basis of transdifferentiation and will advance efforts to exploit this rare phenomenon therapeutically.

scholarly journals Live cell imaging reveals focal adhesions mechanoresponses in mammary epithelial cells under sustained equibiaxial stress

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Lorena Sigaut ◽  
Catalina von Bilderling ◽  
Micaela Bianchi ◽  
Juan Eduardo Burdisso ◽  
Laura Gastaldi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Mammary Epithelial Cells ◽  
Focal Adhesions ◽  
Mammary Epithelial ◽  
Live Cell

scholarly journals Quantitative live cell imaging of nanoparticle translocation into/across lung alveolar epithelial cells

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Arnold Sipos ◽  
Farnoosh Fazlollahi ◽  
Yong Ho Kim ◽  
Robert H. Chow ◽  
Zea Borok ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Live Cell ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial

scholarly journals Thrombospondin-1 mediates distal tubule hypertrophy induced by glycated albumin

2004 ◽  
Vol 379 (1) ◽  
pp. 89-97 ◽  
Author(s):  
Yu-Lin YANG ◽  
Lea-Yea CHUANG ◽  
Jinn-Yuh GUH ◽  
Shu-Fen LIU ◽  
Min-Yuan HUNG ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Renal Tubule ◽  
Distal Tubule ◽  
Renal Hypertrophy ◽  
Cellular Hypertrophy ◽  
Transcription Factor Decoy ◽  
Thrombospondin 1 ◽  
Tubule Cells ◽  
Tgf Β1 ◽  
Distal Renal Tubule

Diabetic nephropathy is characterized by early hypertrophy in both glomerular and tubuloepithelial elements. However, no studies to date have established a direct causal link between hyperglycaemia and renal hypertrophy. Our previous studies have found that high glucose does not induce cellular hypertrophy or expression of TGF-β1 (transforming growth factor-β1) in distal renal tubule cells [Yang, Guh, Yang, Lai, Tsai, Hung, Chang and Chuang (1998) J. Am. Soc. Nephrol. 9, 182–193]. In the present study, we used AGEs (advanced glycation end-products) to mimic long-term hyperglycaemia. Similar to glucose, AGEs did not induce TGF-β1 mRNA in distal renal tubule cells [MDCK (Madin–Darby canine kidney) cells]; however, TGF-β1 bioactivity was increased significantly. This result indicated post-translational regulation. Since TSP-1 (thrombospondin-1) has been demonstrated to activate latent TGF-β1 in a variety of systems, the following experiments were performed. We found that AGEs dose-dependently increased both intracellular and extracellular levels of TSP-1. Purified TSP-1, like AGEs, increased the cellular protein content. Furthermore, anti-TSP-1 neutralizing antibodies attenuated the AGE-induced increase in TGF-β1 bioactivity and hypertrophy. Thus TSP-1 might mediate AGE-induced distal renal tubule hypertrophy. In addition, we observed several putative transcription factor binding sites in the TSP-1 promoter, including those for AP-1 (activator protein-1), CREB (cAMP response element binding protein), NF-κB (nuclear factor-κB), SRF (serum response factor) and HSF (heat-shock factor), by sequence mapping. We used an enhancer assay to screen possible transcription factors involved. We showed that AP-1 and CREB were specifically induced by AGEs; furthermore, TFD (transcription factor decoy) for AP-1 could attenuate the AGE-induced increases in TSP-1 levels and cellular hypertrophy. Thus regulation of TSP-1 might be critical for hyperglycaemic distal tubule hypertrophy. Furthermore, TSP-1 TFD might be a potential approach to ameliorate diabetic renal hypertrophy.

scholarly journals Live cell imaging of the cancer-related transcription factor RUNX2 during mitotic progression

2011 ◽  
Vol 226 (5) ◽  
pp. 1383-1389 ◽  
Author(s):  
Shirwin M. Pockwinse ◽  
Krishna P. Kota ◽  
Alexandre J.C. Quaresma ◽  
Anthony N. Imbalzano ◽  
Jane B. Lian ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Live Cell ◽  
Mitotic Progression ◽  
Related Transcription Factor

scholarly journals Vectorial insertion of apical and basolateral membrane proteins in polarized epithelial cells revealed by quantitative 3D live cell imaging

2006 ◽  
Vol 172 (7) ◽  
pp. 1035-1044 ◽  
Author(s):  
Wei Hua ◽  
David Sheff ◽  
Derek Toomre ◽  
Ira Mellman
Keyword(s):  
Membrane Proteins ◽  
Epithelial Cells ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Fluorescent Protein ◽  
Yellow Fluorescent Protein ◽  
Basolateral Membrane ◽  
Live Cell ◽  
Junctional Complex ◽  
Apical Surface

Although epithelial cells are known to exhibit a polarized distribution of membrane components, the pathways responsible for delivering membrane proteins to their appropriate domains remain unclear. Using an optimized approach to three-dimensional live cell imaging, we have visualized the transport of newly synthesized apical and basolateral membrane proteins in fully polarized filter-grown Madin–Darby canine kidney cells. We performed a detailed quantitative kinetic analysis of trans-Golgi network (TGN) exit, passage through transport intermediates, and arrival at the plasma membrane using cyan/yellow fluorescent protein–tagged glycosylphosphatidylinositol-anchored protein and vesicular stomatitis virus glycoprotein as apical and basolateral reporters, respectively. For both pathways, exit from the TGN was rate limiting. Furthermore, apical and basolateral proteins were targeted directly to their respective membranes, resolving current confusion as to whether sorting occurs on the secretory pathway or only after endocytosis. However, a transcytotic protein did reach the apical surface after a prior appearance basolaterally. Finally, newly synthesized proteins appeared to be delivered to the entire lateral or apical surface, suggesting—contrary to expectations—that there is not a restricted site for vesicle docking or fusion adjacent to the junctional complex.

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