12 - Growth Factor and Hedgehog Signalling Pathways Meet in Developmental Systems

Abstract

This chapter focuses on growth factor and hedgehog signaling pathways in the developmental systems. Signaling pathways in differentiation and morphogenesis are highly conserved systems. Several pathways can be implicated and they converge, cross-react, mutually regulate, and function in combination such as the TGF-β pathway, the hedgehog (Hh), Wnt, Notch, fibroblast growth factor (FGF), and EGF pathways. The Hh genes encode small secreted proteins that participate in intercellular signal transduction associated with a variety of cellular processes. The Hh family is composed of three homologues that include Sonic Hh (Shh), Indian Hh (Ihh), and Desert Hh (Dhh). These occur in the form of precursor proteins. The carboxy (C) terminus of the preprotein has an autocatalytic domain and a signaling domain. The preprotein goes through a process of autocatalytic cleavage resulting in the elimination of the autocatalytic domain. The Hh system is a major signaling pathway in human embryonic development and differentiation. Hh signaling, which is accurately and closely conserved in the evolutionary timescale, is associated with the transduction of signals relating to cell proliferation, embryonic development, and pattern formation. The Hh family proteins are secreted proteins and function in a paracrine mode on their target cells. Hh signaling occurs with the binding of Hh to the glycoprotein called Patched (PTCH1). PTCH binds to the cholesterol-modified N-terminal fragment of Hh. PTCH1 and PTCH2 bind to Hh proteins with similar affinity but PTCH2 is demonstrably a participant in Hh (Dhh) signaling.