The Hedgehog (Hh) pathway is a central pathway from embryonic development to the end of life. Researchers began documenting its power when they discovered it was essential for regeneration of certain animal parts. The zebrafish caudal fin(Quint et al., 2002) and axolotl limbs(Torok et al., 1999;Roy and Gardiner, 2002) of salamanders have been the key animal models. These experiments showed that proper Hh signaling was required in order to obtain normal phenotypes.
The Hh pathway was named when researchers were studying segment polarity genes in drosophila and discovered a mutant that looked like it had hair of a hedgehog. The Hh pathway has been studied in invertebrates such as the drosophila and in vertebrates such as the mouse.(Ingham and McMahon, 2001a) The pathway components are well conserved allowing researchers to gain a great deal of general understanding from vertebrates and invertebrates experiments. The Hh pathway has three protein members: Indian Hedgehog (Ihh), Desert Hedgehog (Dhh), and the most famous Sonic Hedgehog (Shh). Ihh is critical in development of skeletal tissue(Colnot et al., 2005), cartilage(Tiet and Alman, 2003;Schnapp et al., 2005), and cardiac morphogenesis.(Zhang et al., 2001) Dhh has been seen to help in testi formation(Pierucci-Alves et al., 2001), and Schwann cell-derived peripheral nerve sheaths.(Parmantier et al., 1999) Shh affects development of the cerebellum, eyes, gut, hair, heart, limbs, lung, muscle, neurons, pancreas, pituitary, prostate and teeth.(Ingham and McMahon, 2001b)
The Hh proteins act as a mitogen and morphogen.(Vervoort, 2000;Mehlen et al., 2005) At varying concentrations of Hh proteins will cause a wide array of cellular responses. Recently Hh has exhibited long distance diffusion in stable multimeric form.(Goetz et al., 2005) Being a key regulatory pathway in embryonic development, gross defects are seen from animal models to humans with mutations in the pathway. Animal studies are apparent from knock out gene or mutated gene studies. These animal studies have gross defects and often don’t survive. In animals and humans misregulation can lead to holorescphaly(Roessler et al., 1996;Belloni et al., 1996;Chiang et al., 1996;Ming et al., 1998;Wallis and Muenke, 2000;Nasevicius and Ekker, 2000;Hayhurst and McConnell, 2003;Hehr et al., 2004), syndactyly, polydactyl(Hill et al., 2003), and many other birth defects.
The adult Hh pathway is thought to be used during normal tissue maintenance and repair processes.(Harmon et al., 2002;Pasca di and Hebrok, 2003;Beachy et al., 2004) When tissue gets damaged, it has to repair itself. The Hh pathway is then activated and causes Adult Stem Cells (ASC) to divide, just like in ESC. Cancer is widely seen in tissues that are constantly being exposed to the environment, such as skin, smokers lungs, and intestinal lining. All of these tissues have a high risk of cancer and are the most damaged and repaired tissue.