Hedgehog signaling proteins
Wu, Xiaofeng Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas.
Lum, Lawrence Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas.
- Building the Hh pathway using fruit flies
- Atypical molecular switches gate Hh pathway activity
- Cellular tower and Hh signal transduction
- Management of cancer with Hh pathway inhibitors
- Links to Primary Literature
- Additional Readings
An understanding of the molecular programs that control the formation of specific cell types in complex multicellular organisms is essential for therapeutic efforts focused on improving tissue regeneration and disabling cancerous cell growth. The success in characterizing these programs in the last few decades has been largely built on genetic results using the embryonic development of model organisms, such as fruit flies and mice, to identify genes that control cell differentiation. The creation of specific cell types, such as muscle, fat, and blood cells, is a coordinated process dependent on different cellular precursors communicating cell differentiation cues to one another. Perhaps not surprisingly then, many of these molecular programs are controlled by secreted proteins (proteins released from cells) that transmit intercellular signals between neighboring or distant cells. The secreted Hedgehog (Hh) signaling molecule is essential for embryonic patterning and the formation of the limbs and central nervous system. Frequently, as a consequence of genetic mutations, the cellular responses controlled by the Hh protein can be exploited to promote cancerous cell growth. Based on this understanding, chemicals that inhibit these cellular responses have been developed for the treatment of certain forms of skin and brain cancers. This brief overview of the Hh pathway will describe its inception from efforts to understand the molecular basis of development and its remarkable journey to therapeutic relevance in cancer.
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