Chapter 253 - Hedgehog Signaling and Embryonic Development

Abstract

Hh proteins are synthesized as precursor proteins of about 45 kDa. The C-terminal portion of the Hh precursor has autoproteolytic activity and cleaves Hh into a C-terminal peptide of about 25 kDa with no known function and an N-terminal fragment (Hh-N), which constitutes the biologically active portion of Hh. The hedgehog mutation was originally identified in a Drosophila genetic screen as one of the segment-polarity genes important in fly development. Cloning of the hedgehog gene (hh) revealed a secreted peptide whose expression is confined to Engrailed expressing cells and is dependent upon Wingless expression. It is now clear that Hh plays a vital role in the development of multiple organ systems in the fly and vertebrates. In mammals there are three Hh proteins named Sonic Hh (Shh), Desert Hh (Dhh), and Indian Hh (Ihh). Dhh appears to be most closely related to Drosophila Hh, while Shh and Ihh are more closely related to one another. Production and diffusion of these factors in different tissues determines proper development of multiple organ systems.