Indian Hedgehog (Ihh), a member of the Hh family, is a crucial paracrine factor in vertebrate development and homeostasis. It is involved in the Hedgehog (Hh) signaling pathway, which is essential for a variety of developmental events. Ihh plays key roles in regulating chondrocyte proliferation, differentiation, and bone formation, impacting the development of cranial bones, cartilage, and the temporomandibular joint (TMJ) [1].

In Ihh-null mice, symphyseal development was defective due to enhanced chondrocyte maturation and reduced proliferation of chondroprogenitor cells, indicating Ihh signaling is essential for symphyseal cartilage development and anterior mandibular growth [4]. In Sp7-iCre; Ihhfl/fl mice, where Ihh was specifically deleted in Sp7-expressing cells, a dwarfism phenotype with severe skeletal dysplasia and lethality at birth was observed, along with fewer osteoblasts and reduced bone formation-related gene expression, demonstrating Ihh's role in osteoblast differentiation, mineralization, and embryonic osteogenesis [3]. Also, in MPS VII mice, reduced Ihh secretion and response to exogenous Ihh suggested that the reduced proliferation in the growth plate may be due to IHH signaling pathway dysfunction [2].

In conclusion, Ihh is essential for chondrocyte and osteoblast-related development processes. Gene-knockout mouse models, such as Ihh-null, Sp7-iCre; Ihhfl/fl, and MPS VII mice, have been pivotal in revealing Ihh's functions in bone and cartilage development, and understanding how its dysregulation may contribute to skeletal-related diseases.