A Prickly Subject: Apoptotic Regulation by Hedgehog Morphogens

Abstract

Morphogens, as intercellular signalling proteins, provide a non-cell-autonomous mechanism to impart positional information to cells and govern essential cellular processes such as apoptosis. Individual morphogen pathways utilise diverse strategies to regulate the assembly and activity of the pro-apoptotic multi-protein complexes -namely the apoptosome and the death-inducing signalling complex (DISC). This review aims to highlight the apoptotic regulatory mechanisms utilised by the Hedgehog (HH) morphogen pathway -with particular emphasis on a novel Caspase-9 activating complex and the utilisation of a pro-apoptotic autocrine-signalling loop.

A Joint Less Ordinary: Intriguing Roles for Hedgehog Signalling in the Development of the Temporomandibular Synovial Joint

“…The fact that Gli2 or Gli3 null embryos exhibited non-identical phenotypes [ 58 , 63 ] in distinct tissues supports the possibility of distinct roles for different downstream effectors. These data also suggested a potential contribution of Hh pathway effectors other than GLI2/3, with non-canonical Hh pathway effectors being likely candidates [ 64 , 65 , 66 ]. Nevertheless, these data do support a significant contribution of GLI2 and GLI3-associated functions in the Ihh null phenotype.…”

“…One explanation resides in the retention of Smo signalling within (i) a small number of those Sox9 -expressing cells that either failed to recombine the floxed Smo allele and/or (ii) a cell population derived from a non- Sox9 -expressing lineage. More controversially, it could also indicate important contributions from non-canonical signalling upstream of Smo and downstream of Ihh [ 64 , 65 , 66 ]. Overall, these results partially supported a role for Smo-associated signalling in the maturation of the articular disc/cavity space.…”

“…Two important elements currently missing from our understanding of TMJ development are (i) the signal transductions pathways that initiate, maintain and restrain Ihh expression and (ii) the potential contribution of non-canonical Hh signalling [ 64 , 65 , 66 ]. Going forward, it will be important to apply consistent methodological means to perturb gene function and analyse the outcomes.…”