Disease relevance of Dhh

• This study examined whether SHH, 2 other ligands IHH and Desert hedgehog, and receptors or downstream targets are expressed in normal gastric epithelium or in intestinal and diffuse-type gastric cancers [1].
• In addition, we observed Shh and Dhh transgenic skin from both phenotypes developed lesions reminiscent of human basal cell carcinoma (BCC), indicating that BCCs can be generated despite the loss of much of the proliferative (basal) compartment [2].
• Two distinct novel phenotypes were observed amongst Shh and Dhh transgenics, one exhibiting epidermal progenitor cell hyperplasia with the other displaying a complete loss of epidermal tissue renewal indicating deregulation of stem cell activity [2].
• Based on observations that deletion of one of the three Hh genes, Dhh, leads to male infertility, we hypothesized that regulated expression of Hh signalling components would be a feature of adult spermatogenesis [3].
• Desert hedgehog-patched 2 expression in peripheral nerves during Wallerian degeneration and regeneration [4].

High impact information on Dhh

• Analysis of Dhh(-/-) XY gonads revealed that differentiation of fetal Leydig cells was severely defective [5].
• Defects in Leydig cell differentiation in Dhh(-/-) XY gonads did not result from failure of cell migration from the mesonephros, thought to be a possible source of Leydig cell precursors [5].
• Nor did DHH/PTCH1 signaling appear to be involved in the proliferation or survival of fetal Leydig precursors in the interstitium of the XY gonad [5].
• In nerve fibroblasts, Dhh upregulates ptc and hedgehog-interacting protein (hip) [6].
• Schwann cell-derived Desert hedgehog controls the development of peripheral nerve sheaths [6].

Biological context of Dhh

• Rat Dhh complete coding sequence (CDS) was determined by assembling nucleotide positions 426397-426963, 429715-429976 and 430244-430898 of the AC114446.3 genome sequence [7].
• Here, we identified and characterized rat Dhh and Ihh genes by using bioinformatics [7].
• Thus the elucidation of Shh (and Dhh) target gene activation in the skin will likely identify those genes responsible for increasing the proliferative potential of epidermal basal cells and the mechanisms involved in regulating epidermal stem cell fate [2].
• Analysis of a null mutant demonstrates that Dhh signaling plays an essential role in the regulation of mammalian spermatogenesis [8].
• However, nothing is known of the roles of Dhh or Ihh, nor of the possible function of Shh during later embryogenesis [9].

Anatomical context of Dhh

• However, in a chick embryo digit duplication assay used to measure polarizing activity, Ihh was the least active, and Dhh was almost as potent as Shh [10].
• Rat Dhh mRNA was expressed in prostate, duodenum and dorsal root ganglia, while rat Ihh mRNA was expressed in cartilage [7].
• Examination of the developing testis in different genetic backgrounds suggests that Dhh regulates both early and late stages of spermatogenesis [8].
• As Desert hedgehog (Dhh) is involved in the development of peripheral nerves and is expressed in adult nerves, it may play a role in the maintenance of adult nerves and degeneration and regeneration after injury [4].
• Desert hedgehog (Dhh) gene is required in the mouse testis for formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules [11].

Associations of Dhh with chemical compounds

• These behavioral abnormalities of Dhh KO male mice may be due to lower testosterone levels with abnormal development of the testes caused by Dhh-null mutation [12].

Other interactions of Dhh

• These findings suggest that a mechanism for fine-tuning the biological actions of Shh, Ihh, and Dhh, exists beyond the simple temporal and spatial control of their expression domains within the developing and adult organism [10].
• These phenotypes associated also with the decreased expression of Sox9, Desert hedgehog, Hsd3beta, Platelet/endothelial cell adhesion molecule, and alpha-smooth muscle actin, which are markers of the Sertoli, Leydig, endothelial, and peritubular myoid cells of the developing testis [13].
• The expression of Patched is lost in Dhh mutants [8].
• Dhh expression is initiated in Sertoli cell precursors shortly after the activation of Sry and persists in the testis into the adult [8].
• These results suggest that the Dhh-Ptc2 signaling pathway may be involved in the maintenance of adult nerves and may be one of the factors that directly or indirectly determines the response of peripheral nerves to injury [4].

Analytical, diagnostic and therapeutic context of Dhh

• The Dhh receptor patched(ptc)2 was detected in adult sciatic nerves using RT-PCR, however, ptc1 was undetectable under the same experimental condition [4].
• In Desert hedgehog knockout mice, the connective tissue sheaths in adult nerves appear highly abnormal by electron microscopy [14].

References