Sonic hedgehog signalling pathway: a complex network

Abstract

Sonic Hedgehog (Shh) signalling cascade is one of the intricate signal transduction mechanisms that govern the precisely regulated developmental processes of multicellular organisms. Along with establishing the patterns of cellular differentiation to direct complex organ formation, it also has an important role in post-embryonic tissue regeneration and repair processes. Especially, Shh signalling is implicated in the induction of multifarious neuronal populations in central nervous system. There is compelling evidence of the involvement of Shh protein in the signalling network that regulates various morphogenetic processes such as the exquisite neural tube pattern formation. In the morphogenetic field, the activation of Shh signalling processes is intricately linked to the alterations at the molecular level in the structure of Shh protein that leads to its altered biophysical and biochemical reactivity. This brief article gives an overview of such complex cascade of events in Shh signalling and its transduction pathways.

Keywords: Autoproteolysis; Holoprosencephaly; Lipidation; Neural tube pattern; Notochord; Sonic hedgehog.

Fig. 1:

Schematically represented alteration of ventral neuronal fate induced by different concentrations of Shh protein. D, dorsal neural tube; V, ventral neural tube; MN, motor neurons, FP, floor plates; Shh, Sonic Hedgehog. (Reproduced with permissions from Reference 12).

Fig. 2:

Schematic representation of dual lipid modification of Shh protein.

Fig. 3:

The Sonic Hedghehog (Shh) signalling pathway: Activation of signalling pathway is connected to various transmembrane proteins (Ptc, Smo), transcription factors (Ci/Gli) and protein kinases (Su(fu), fu) (Reproduced with permissions from Reference 31).