TGF-β Superfamily Signaling in Embryonic Development and Homeostasis

Abstract

TGF-beta superfamily signaling pathways emerged with the evolution of multicellular animals, suggesting that these pathways contribute to the increased diversity and complexity required for the development and homeostasis of these organisms. In this review we begin by exploring some key developmental and disease processes requiring TGF-beta ligands to underscore the fundamental importance of these pathways before delving into the molecular mechanism of signal transduction, focusing on recent findings. Finally, we discuss how these ligands act as morphogens, how their activity and signaling range is regulated, and how they interact with other signaling pathways to achieve their specific and varied functional roles.

MicroRNA 483-3p suppresses the expression of DPC4/Smad4 in pancreatic cancer

“…The TGF-b superfamily members are cytokines that play key roles in regulating adult tissue homeostasis, and deregulation of its signaling pathway has been associated with various carcinogenesis [36,37]. Smad4 is the common Smad protein (Co-Smad), together with phosphorylated R-Smads (receptor-regulated Smads), that mediates the transduction and response of TGF-b and BMP signal [20,26].…”

TGF-β Family Signaling in Neural and Neuronal Differentiation, Development, and Function

“…Zebrafish use a different miRNA, miR-430, to target nodal signaling (Choi et al 2007). Taken together, these studies identify a fundamental role for BMP and nodal signaling in neural induction and indicate that these families of antagonists act in a redundant or compensatory manner (Piccolo et al 1999;Niehrs 2001;Wu and Hill 2009). Epidermal fate is determined by the expression of the BMP-related Decapentaplegic (Dpp) in Drosophila and BMP-4 in Xenopus explants (Wilson and Hemmati-Brivanlou 1995).…”

Activin/Nodal signalling before implantation: setting the stage for embryo patterning

“…chromatin modifiers recruited by Smad complexes and their cofactors. These advances have been the subject of several reviews [10][11][12].…”

“…Further interactions between the two signalling pathways involve the inhibitory Smads, Smad6 and Smad7, which are themselves targets of Smad signalling and act either as general inhibitors of Smad-mediated signalling (Smad7), or inhibit more specifically the BMP pathway (Smad6) [27]. Smads can also integrate the input of FGF/RTK signalling, via MAPK-mediated phosphorylation, which can, for example, promote Smad1 degradation, and reduce BMP signal transduction [12,28]. Further information on how Smads integrate input from other signalling pathways can be found in other reviews [7,10,29].…”