Abstract
Tumor necrosis factor alpha (TNF-α) plays important roles in processes such as immunomodulation, fever, inflammatory response, inhibition of tumor formation, and inhibition of viral replication. TNF-α and its receptors are ubiquitously expressed in developing organs and they regulate the survival, proliferation, and apoptosis of embryonic stem cells (ESCs) and progenitor cells. TNF-α is an important inflammatory factor that also regulates the inflammatory response during organogenesis, and its cytotoxic effects can interfere with normal developmental processes, even leading to the onset of diseases. This review summarizes the various roles of TNF-α in organogenesis in terms of its secreting pattern, concentration-dependent activities, and interactions with other signaling pathways. We also explored new potential functions of TNF-α.
Highlights
Tumor necrosis factor alpha (TNF-α) belongs to the TNF superfamily (Aggarwal, 2003) of proteins with highly similar structures and conserved interaction profiles (Bodmer et al, 2002)
Pro-TNF exhibits biological activities; for instance, the homolog of pro-TNF, Eiger, induces apoptosis in compound eyes of Drosophila by activating the c-Jun N-terminal kinases (JNKs) signaling pathway (Igaki et al, 2002), and concentric cardiac hypertrophy occurs in transgenic mice with up-regulated pro-TNF expression (Dibbs et al, 2003)
TNF-α plays a central role in the process of neurogenesis in embryos and neonates by regulating the survival, proliferation, and differentiation of neural progenitor cells (NPCs) (Bernardino et al, 2008; Lan et al, 2012)
Summary
Reviewed by: Yasutaka Okabe, Osaka University, Japan Hiroyasu Kidoya, Osaka University, Japan. Specialty section: This article was submitted to Morphogenesis and Patterning, a section of the journal Frontiers in Cell and Developmental. Tumor necrosis factor alpha (TNF-α) plays important roles in processes such as immunomodulation, fever, inflammatory response, inhibition of tumor formation, and inhibition of viral replication. TNF-α and its receptors are ubiquitously expressed in developing organs and they regulate the survival, proliferation, and apoptosis of embryonic stem cells (ESCs) and progenitor cells. TNF-α is an important inflammatory factor that regulates the inflammatory response during organogenesis, and its cytotoxic effects can interfere with normal developmental processes, even leading to the onset of diseases. This review summarizes the various roles of TNF-α in organogenesis in terms of its secreting pattern, concentration-dependent activities, and interactions with other signaling pathways. We explored new potential functions of TNF-α
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