Abstract
The Sonic hedgehog (SHH) signaling pathway is essential for embryonic development and tissue regeneration. The dysfunction of SHH pathway is involved in a variety of diseases, including cancer, birth defects, and other diseases. Here we reviewed recent studies on main molecules involved in the SHH signaling pathway, specifically focused on their function in epithelial tissue and appendages development, including epidermis, touch dome, hair, sebaceous gland, mammary gland, tooth, nail, gastric epithelium, and intestinal epithelium. The advance in understanding the SHH signaling pathway will give us more clues to the mechanisms of tissue repair and regeneration, as well as the development of new treatment for diseases related to dysregulation of SHH signaling pathway.
Highlights
1.1 Sonic hedgehog (SHH) signaling pathwayIn the development of invertebrates and vertebrates, the members of the hedgehog (HH) signaling family mediate many essential processes, including short-term and long-term modeling
The conduction of SHH signaling pathway requires the participation of many proteins and factors (Tab. 1), mainly including SHH, PTC receptors (PTC1, PTC2), Smoothened receptor (SMO), Kinesin Family member7 (KIF7), Suppressor of fused homolog (SUFU), Protein Kinase A (PKA), and GLI transcription factors (GLI1, GLI2, GLI3) [130] (Fig. 1)
CDON and interference hedgehog (IHOG) are similar in function, IHOG binds to a different surface near the second HH helix, and this interaction requires heparin, which connects two binding partners, and promotes IHOG dimerization [67], whereas CDON and brother of CDON (BOC) can each directly bind to SHH
Summary
In the development of invertebrates and vertebrates, the members of the hedgehog (HH) signaling family mediate many essential processes, including short-term and long-term modeling. The SHH pathway should be off at most of the time, by the inhibition of specific factors such as Patched 1 (PTC1), Protein Kinase A (PKA), Casein Kinase (CK1), and Glycogen Synthase Kinase 3 beta (GSK3b), and only valid at precise time points [98] It plays a biological role by terminating the factor of glioma-associated oncogene (Gli) [144]. IHH signal induces activation of Parathyroid Hormone-related Protein (PTHRP) on the articular surface and gets rid of the hypertrophy of chondrocytes [49] It participates in endochondral bone formation as a negative regulator of chondrocyte differentiation in mouse [131] and is involved in the development of. SHH and DHH act synergistically [114]; In the Dhh-mutant epididymis, SHH plays a compensatory role in order to maintain the stability of the signaling pathway [21]
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