β-catenin has an ancestral role in cell fate specification but not cell adhesion

AbstractThe ß-catenin protein has two major known functions in animal cells. It keeps epithelial tissue homeostasis by its connection with Adherens Junctions (AJ), and it serves as a transcriptional cofactor along with Lef/Tcf to enter the nucleus and regulate target genes of the Wnt/ß-catenin (cWnt) signaling pathway. To assess the ancestral role of ß-catenin during development we examined its distribution and function in the ctenophore Mnemiopsis leidyi (one of the earliest branching animal phyla) by using ctenophore-specific antibodies and mRNA injection. We found that ß-catenin protein never localizes to cell-cell contacts during embryogenesis as it does in other metazoans, most likely because ctenophore-cadherins do not have the cytoplasmic domain required for interaction with the catenin proteins. Downregulation of zygotic Mlß-catenin signaling led to the loss of endodermal and mesodermal tissues indicating that nuclear ß-catenin may have a deep role in germ-layer evolution. Our results indicate that the ancestral role for ß-catenin was in the cell-fate specification and not in cell adhesion and also further emphasizes the critical role of this protein in the evolution of tissue layers in metazoans.

Download Full-text

Genes necessary for C. elegans cell and growth cone migrations

Development ◽

10.1242/dev.124.9.1831 ◽

1997 ◽

Vol 124 (9) ◽

pp. 1831-1843 ◽

Cited By ~ 20

Author(s):

W.C. Forrester ◽

G. Garriga

Keyword(s):

Cell Fate ◽

Single Gene ◽

Growth Cones ◽

Cell Fate Specification ◽

Fate Specification ◽

C Elegans ◽

Final Destination ◽

Multiple Cell

The migrations of cells and growth cones contribute to form and pattern during metazoan development. To study the mechanisms that regulate cell motility, we have screened for C. elegans mutants defective in the posteriorly directed migrations of the canal-associated neurons (CANs). Here we describe 14 genes necessary for CAN cell migration. Our characterization of the mutants has led to three conclusions. First, the mutations define three gene classes: genes necessary for cell fate specification, genes necessary for multiple cell migrations and a single gene necessary for final positioning of migrating cells. Second, cell interactions between the CAN and HSN, a neuron that migrates anteriorly to a position adjacent to the CAN, control the final destination of the HSN cell body. Third, C. elegans larval development requires the CANs. In the absence of CAN function, larvae arrest development, with excess fluid accumulating in their pseudocoeloms. This phenotype may reflect a role of the CANs in osmoregulation.

Download Full-text

Cell Delivery and Recirculation

Tissue Engineering ◽

10.1093/oso/9780195141306.003.0016 ◽

2004 ◽

Author(s):

W. Mark Saltzman

Keyword(s):

Tissue Engineering ◽

Cell Adhesion ◽

Cell Fate ◽

Critical Role ◽

Cell Movement ◽

The Body ◽

Associated Proteins ◽

Adult Organism ◽

Adenine Deaminase

Perhaps the simplest realization of tissue engineering involves the direct administration of a suspension of engineered cells—cells that have been isolated, characterized, manipulated, and amplified outside of the body. One can imagine engineering diverse and useful properties into the injected cells: functional enzymes, secretion of drugs, resistance to immune recognition, and growth control. We are most familiar with methods for manipulating the cell internal chemistry by introduction or removal of genes; for example, the first gene therapy experiments involved cells that were engineered to produce a deficient enzyme, adenine deaminase (see Chapter 2). But genes also encode systems that enable cell movement, cell mechanics, and cell adhesion. Conceivably, these systems can be modified to direct the interactions of an administered cell with its new host. For example, cell adhesion signals could be introduced to provide tissue targeting, cytoskeleton-associated proteins could be added to alter viscosity and deformability (in order to prolong circulation time), and motor proteins could be added to facilitate cell migration. Ideally, cell fate would also be engineered, so that the cell would move to the appropriate location in the body, no matter how it was administered; for example, transfused liver cells would circulate in the blood and, eventually, crawl into the liver parenchyma. Cells find their place in developing organisms by a variety of chemotactic and adhesive signals, but can these same signaling mechanisms be engaged to target cells administered to an adult organism? We have already considered the critical role of cell movement in development in Chapter 3. In this chapter, the utility of cell trafficking in tissue engineering is approached by first considering the normal role of cell recirculation and trafficking within the adult organism. Most cells can be easily introduced into the body by intravenous injection or infusion. This procedure is particularly appropriate for cells that function within the circulation; for example, red blood cells (RBCs) and lymphocytes. The first blood transfusions into humans were performed by Jean-Baptiste Denis, a French physician, in 1667. This early appearance of transfusion is startling, since the circulatory system was described by William Harvey only a few decades earlier, in 1628.

Download Full-text

Stem Cell Fate Specification: Role of Master Regulatory Switch Transcription Factor PU.1 in Differential Hematopoiesis

Stem Cells and Development ◽

10.1089/scd.2005.14.140 ◽

2005 ◽

Vol 14 (2) ◽

pp. 140-152 ◽

Cited By ~ 31

Author(s):

Gurudutta U. Gangenahalli ◽

Pallavi Gupta ◽

Daman Saluja ◽

Yogesh K. Verma ◽

Vimal Kishore ◽

...

Keyword(s):

Transcription Factor ◽

Stem Cell ◽

Cell Fate ◽

Cell Fate Specification ◽

Stem Cell Fate ◽

Fate Specification

Download Full-text

The role of the Rx homeobox gene in retinal progenitor proliferation and cell fate specification

Mechanisms of Development ◽

10.1016/j.mod.2018.04.003 ◽

2018 ◽

Vol 151 ◽

pp. 18-29 ◽

Cited By ~ 6

Author(s):

H.M. Rodgers ◽

V.J. Huffman ◽

V.A. Voronina ◽

M. Lewandoski ◽

P.H. Mathers

Keyword(s):

Cell Fate ◽

Homeobox Gene ◽

Cell Fate Specification ◽

Fate Specification ◽

Retinal Progenitor

Download Full-text

T1728 Role of ADAM10 Signaling in Cell Proliferation and Cell Fate Specification is Conserved Between the Developing and Adult Intestine

Gastroenterology ◽

10.1016/s0016-5085(10)62606-6 ◽

2010 ◽

Vol 138 (5) ◽

pp. S-566 ◽

Cited By ~ 2

Author(s):

Yu-Hwai Tsai ◽

Kelli L. VanDussen ◽

Howard C. Crawford ◽

Linda C. Samuelson ◽

Peter J. Dempsey

Keyword(s):

Cell Proliferation ◽

Cell Fate ◽

Cell Fate Specification ◽

Fate Specification

Download Full-text

Role of Amyloid Precursor Protein (APP) and Its Derivatives in the Biology and Cell Fate Specification of Neural Stem Cells

Molecular Neurobiology ◽

10.1007/s12035-018-0914-2 ◽

2018 ◽

Vol 55 (9) ◽

pp. 7107-7117 ◽

Cited By ~ 17

Author(s):

Raquel Coronel ◽

Adela Bernabeu-Zornoza ◽

Charlotte Palmer ◽

Mar Muñiz-Moreno ◽

Alberto Zambrano ◽

...

Keyword(s):

Stem Cells ◽

Neural Stem Cells ◽

Amyloid Precursor Protein ◽

Cell Fate ◽

Precursor Protein ◽

Cell Fate Specification ◽

Fate Specification

Download Full-text

The Protective Roles of ROS-Mediated Mitophagy on125I Seeds Radiation Induced Cell Death in HCT116 Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/9460462 ◽

2016 ◽

Vol 2016 ◽

pp. 1-18 ◽

Cited By ~ 16

Author(s):

Lelin Hu ◽

Hao Wang ◽

Li Huang ◽

Yong Zhao ◽

Junjie Wang

Keyword(s):

Cell Fate ◽

Target Genes ◽

Radiation Treatment ◽

Tumor Therapy ◽

Critical Role ◽

Mitochondrial Ros ◽

Intracellular Ros ◽

Radiation Induced ◽

Hct116 Cells

For many unresectable carcinomas and locally recurrent cancers (LRC),125I seeds brachytherapy is a feasible, effective, and safe treatment. Several studies have shown that125I seeds radiation exerts anticancer activity by triggering DNA damage. However, recent evidence shows mitochondrial quality to be another crucial determinant of cell fate, with mitophagy playing a central role in this control mechanism. Herein, we found that125I seeds irradiation injured mitochondria, leading to significantly elevated mitochondrial and intracellular ROS (reactive oxygen species) levels in HCT116 cells. The accumulation of mitochondrial ROS increased the expression of HIF-1αand its target genes BINP3 and NIX (BINP3L), which subsequently triggered mitophagy. Importantly,125I seeds radiation induced mitophagy promoted cells survival and protected HCT116 cells from apoptosis. These results collectively indicated that125I seeds radiation triggered mitophagy by upregulating the level of ROS to promote cellular homeostasis and survival. The present study uncovered the critical role of mitophagy in modulating the sensitivity of tumor cells to radiation therapy and suggested that chemotherapy targeting on mitophagy might improve the efficiency of125I seeds radiation treatment, which might be of clinical significance in tumor therapy.

Download Full-text