1. Watch out for these!! BCC may appear as skin bump or growth that is:
Pearly or waxy
White or light pink
Flesh-colored or brown
Skin can be slightly raised or flat
Sore that bleeds easily or doesn’t heal
Treatment varies according to location, size, and depth of area
Excision
Curettage and electrodesiccation
Surgery
Cryosurgery
Radiation
Skin creams treat superficial cases; pharmacologic agents that mimic the effect of patched form the basis for these topical treatments

2. How is the body plan specified?
Egg ---> animal
in 24 hours! 4

3. signaling specify cell fates in
Wingless and Hedgehog
signaling specify cell fates in
the ventral epidermis
wild type
arm mutant

4. Engrailed is expressed by cells posterior to those that express
Wingless
Anterior
Posterior Wg En

5. Genetics
revealed the
ligand and
proteins in
the signal
transduction
pathway

6. This pathway has interesting parallels to the Wnt pathway
Frizzled relative
Patched is an inhibitor of Smoothened, a 7-transmembrane protein
Downstream of Smoothened is a signaling complex with the transcription factor Cubitus interruptus (Ci), a serine/threonine kinase (Fused), kinesin like molecule called Costal 2, and suppressor of fused (Sufu)
Complex phophorylates Ci or Gli and causes its ubiquitination, but instead of being cut into little pieces, gets cut into big piece that acts as a repressor of transcription
Regulated ubiqitination
Of a transcription factor

7. Here it is in “a little” more detail

8. It’s now not a surprise
That we also
have this same pathway
And it regulates
mammalian development

9. As one of the big five it regulates
development of most organs and tissues

10. And pathway activation occurs in several human cancers

11. And this story led from flies to mice to cancer to sheep to drugs!

12. The Smo antagonist vismodegib is an effective BCC therapy.
The Smo antagonist vismodegib is an effective BCC therapy. (A) Multiple untreated, but biopsy proven, BCC tumors in an individual with a genetic syndrome leading to Shh overexpression. (B) Vismodegib-treated tumors shrink, but several resistant tumors remain after 1 yr of drug treatment. Image courtesy of A.L.S. Chang.
Atwood S X et al. J Cell Biol 2012;199:
© 2012 Atwood et al.

13. We still don’t know how Patched inhibits Smoothened
But here’s one current theory

14. In mammals Hedgehog signaling
occurs in the primary cilium!

15. Another theory suggests Patched inhibits Smootehned
By regulating its transport into the cilium