12 Hedgehog Signaling
in Animal Development
and Human Disease
E. C. Bailey, M. P. Scott, and R. L. Johnson
12.1
Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 211
12.2 Reception of the Hh Signal. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 212
12.3 Hh Signal Transmission from the Cytosol to the Nucleus . . . . . .. 216
12.4 Hh Signaling in Disease and Tumorigenesis ................. 219
12.5 The Role of Cholesterol in Hh Signaling . . . . . . . . . . . . . . . . . . .. 223
12.6 Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 226
References .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 227
12.1 Introduction
Higher eukaryotes have developed a number of mechanisms to address
the challenge of progressing from a single-cell zygote to a multicellular
adult organism. Forming complex structures such as a wing, eye, or a
spinal cord requires precise control of cell growth and differentiation.
Generating spatial patterns in embryogenesis requires communication
between adjacent cells, and secreted proteins are one way by which
neighboring cells relay information. The Hedgehog (Hh) family of
secreted proteins is critical for the embryonic development of many
animals. Hh signaling mechanisms thus provide a window into early
development and pattern formation. Genetic screens using Drosophila
have revealed a number of components involved in Hh signaling. For
many of them, their vertebrate counterparts have been found and this