Modeling the Role of Wnt Signaling in Human and Drosophila Stem Cells

Abstract

The discovery of induced pluripotent stem (iPS) cells, barely more than a decade ago, dramatically transformed the study of stem cells and introduced a completely new way to approach many human health concerns. Although advances have pushed the field forward, human application remains some years away, in part due to the need for an in-depth mechanistic understanding. The role of Wnts in stem cells predates the discovery of iPS cells with Wnts established as major pluripotency promoting factors. Most work to date has been done using mouse and tissue culture models and few attempts have been made in other model organisms, but the recent combination of clustered regularly interspaced short palindromic repeats (CRISPR) gene editing with iPS cell technology provides a perfect avenue for exploring iPS cells in model organisms. Drosophila is an ideal organism for such studies, but fly iPS cells have not yet been made. In this opinion article, we draw parallels between Wnt signaling in human and Drosophila stem cell systems, propose ways to obtain Drosophila iPS cells, and suggest ways to exploit the versatility of the Drosophila system for future stem cell studies.

WNT Signaling in Disease

“…The WNT signaling pathway is an evolutionarily conserved signal transduction pathway that regulates a wide range of cellular functions during development and adulthood. It controls multiple aspects of development, including cell proliferation, cell fate determination, apoptosis, cell migration and cell polarity during development and stem cell maintenance in adults [1,2,3]. Inappropriate activation of the WNT pathway is also a major factor in human oncogenesis [4].…”

Extrinsic Regulators of mRNA Translation in Developing Brain: Story of WNTs

“…The WNT signaling pathway is an evolutionarily conserved signal transduction pathway that regulates a wide range of cellular functions including cell proliferation, cell fate determination, apoptosis, cell migration, and cell polarity during development and stem cell maintenance in adults [ 68 , 69 , 70 ]. WNT proteins are lipid-modified glycoproteins that are about 350–400 amino acids in length [ 71 ] and act as ligands that interact with Frizzled (FZD) receptors which are located on the cell surface, to activate intracellular signaling pathways [ 71 , 72 , 73 ].…”

RpS13 controls the homeostasis of germline stem cell niche through Rho1‐mediated signals in the Drosophila testis

“…The classical Wnt/β-catenin (β-catenin is also called Arm in Drosophila) pathway primarily regulates cell fate determination during development. 8 Shifting the Arm protein from the cadherin bound pool to the cytoplasmic pool can increase the amount of available Arm protein for the activation of downstream target genes. 9 As a multifunctional protein, Arm can interact with cadherin in cell adhesions to form a link with the actin cytoskeleton.…”

“…9,10 Moreover, the non-classical Wnt signalling pathway mainly regulates cytoskeletal organization and has been classified as two independent pathways (Wnt/JNK and Wnt/calcium) depending on their major intracellular mediators. 8,11 The small GTPases of the Rho family, including Rac1, Cdc42 and Rho1, are involved in the non-classical Wnt signalling pathway. Rho GTPases act as a molecular switch participating in several physiological activities such as cell migration, cell adhesion, cytokinesis, cell proliferation, apoptosis and differentiation.…”