SHHsignaalit

Shhsignaalit, or Sonic hedgehog (SHH) signaling, is a conserved cellular communication pathway essential for embryonic development and tissue patterning in vertebrates. The SHH pathway regulates cell fate, proliferation, and differentiation by conveying positional information through morphogen gradients. The pathway derives its name from a vertebrate homolog of the original Drosophila hedgehog gene, which was named Sonic hedgehog after a video game character.

Core components of the SHH pathway include the SHH ligand, the Patched receptors (PTCH1/2), the signal transducer Smoothened (SMO), and the GLI family of transcription factors (GLI1, GLI2, GLI3). In the absence of SHH, PTCH inhibits SMO, leading to processing of GLI proteins into repressor forms and suppression of SHH target genes. When SHH binds PTCH, SMO activity is relieved, GLI factors are activated, and target genes promoting growth and patterning are expressed. The primary cilium serves as a critical hub for signal transduction, with SUFU acting as a regulator of GLI activity.

SHH signaling plays a central role in anterior-posterior patterning of the neural tube, limb development, brain morphogenesis, and organ formation. It interacts with other signaling networks, including BMP, WNT, and FGF pathways, to orchestrate coordinated development.

Dysregulation of SHH signaling is linked to disease. Loss-of-function mutations can cause holoprosencephaly and congenital malformations, while gain-of-function or constitutive activation is associated with cancers such as basal cell carcinoma and medulloblastoma. Therapeutic interventions target the pathway, notably SMO inhibitors like vismodegib and sonidegib, with resistance arising through downstream mutations in GLI factors or alternative pathway activation.