DHH

dHh, or Drosophila hedgehog, is a secreted signaling protein and the founding ligand of the Hedgehog (Hh) pathway in the fruit fly Drosophila melanogaster. The hedgehog gene was identified for its distinctive denticle-containing phenotype in mutant embryos, which gave rise to the gene name and to the broader Hedgehog signaling paradigm used in developmental biology.

The Hedgehog precursor is synthesized as a ~45 kDa protein that undergoes autoproteolytic cleavage to generate an active N-terminal signaling fragment (Hh-N) and a C-terminal fragment that participates in the processing reaction. The Hh-N signaling molecule is modified by two lipid attachments: a palmitoyl group added to the N-terminus and a cholesterol moiety covalently attached to the C-terminus during processing. These lipid modifications enhance signaling potency and influence the distribution of Hh-N by restricting diffusion and promoting ligand multimerization and association with lipoprotein particles and extracellular matrix components.

In Drosophila, Hh-N binds to the Patched (Ptc) receptor, relieving Ptc-mediated inhibition of Smoothened (Smo) and triggering a signal transduction cascade that regulates the activity of the Cubitus interruptus (Ci) transcription factor. The resulting transcriptional program controls patterning and growth in multiple tissues, including the embryonic axis and adult wing imaginal discs.

dHh is the Drosophila ortholog of vertebrate Hedgehog proteins, such as Sonic Hedgehog (Shh). While the core signaling logic is conserved, the pathway components and regulatory details show species-specific differences. The dHh system remains a central model for studying morphogen gradients, signal transduction, and developmental patterning.