ABSTRACT
A large amount of data collected during the past one hundred years has established that vitamin A (also known as retinol) and its derivatives, the retinoids (Figure 1.1), play crucial roles during vertebrate development. The retinoids are fat-soluble morphogens that are involved in a variety of processes, such as pattern formation during early development as well as in organogenesis, cell proliferation, cell differentiation, apoptosis, vision, immune responses, and tissue homeostasis (Blomhoff and Blomhoff 2006, Campo-Paysaa et al. 2008, Collins and Mao 1999, Duester 2008, Glover et al. 2006, Hall et al. 2011, Mark et al. 2006, Niederreither and Dollé 2008,
1.1 Introduction ......................................................................................................1 1.2 Retinoid Metabolism ........................................................................................4 1.3 Classical Retinoid Signal Transduction: The RXR/RAR Heterodimer ...........7 1.4 Non-Classical Retinoid Signal Transduction ....................................................8 1.5 Retinoid Functions during Development ........................................................ 10
1.5.1 Central Nervous System Patterning Driven by RA ............................ 10 1.5.2 RA Signaling in Neural Crest Cells (NCCs) and Placode
Development ....................................................................................... 12 1.5.3 RA Signaling and Left/Right (LR) Axial Patterning ......................... 13 1.5.4 RA Signaling in Somitogenesis .......................................................... 13 1.5.5 RA in Heart Field Specication ......................................................... 13 1.5.6 RA Signaling and Kidney Development ............................................ 14 1.5.7 Relevance of RA Signaling for Body Appendage Development ........ 14 1.5.8 Endoderm Specication and RA ........................................................ 15
1.6 Evolution of RA Signaling .............................................................................. 15 1.6.1 Chordate RA Signaling....................................................................... 16 1.6.2 Non-Chordate RA Signaling .............................................................. 18
1.7 Conclusion ...................................................................................................... 19 Acknowledgements ..................................................................................................20 References ................................................................................................................20
Noy 2010, Theodosiou et al. 2010). Initial insights into retinol-dependent developmental processes were obtained from nutritional excess and deciency studies carried out in different animal models including pigs and rats (Hale 1933, Wilson and Warkany 1949). In particular, the so-called vitamin A deciency (VAD) models produced valuable information about the biological roles of retinol in different organs during embryonic development (Wilson et al. 1953). The subsequent emergence of genetic and molecular tools allowed a much more detailed dissection of the developmental functions of retinol and its derivatives including the identication of the molecular machinery underlying retinoid-dependent signaling (Giguere et al. 1987, Mark et al. 2006, Petkovich et al. 1987).
