Abstract
ABSTRACTThe patterning activity of a morphogen depends on secretion and dispersal mechanisms that shape its distribution to the cells of a receptive field. In the case of the protein Hedgehog (Hh), these mechanisms of secretion and transmission remain unclear. In the developing Drosophila visual system, Hh is partitioned for release at opposite poles of photoreceptor neurons. Release into the retina regulates the progression of eye development; axon transport and release at axon termini trigger the development of postsynaptic neurons in the brain. Here we show that this binary targeting decision is controlled by a C-terminal proteolysis. Hh with an intact C-terminus undergoes axonal transport, whereas a C-terminal proteolysis enables Hh to remain in the retina, creating a balance between eye and brain development. Thus, we define a novel mechanism for the apical/basal targeting of this developmentally important protein and posit that similar post-translational regulation could underlie the polarity of related ligands.
Highlights
The Hedgehog (Hh) family encodes secreted morphogens with roles in patterning, stem cell maintenance and neoplastic disease (Jiang and Hui, 2008; Scales and de Sauvage, 2009; Varjosalo and Taipale, 2008)
The two polypeptides, HhC16 and HhC24, were observed with an additional anti-Hh antibody (Tabata and Kornberg, 1994) and after the expression of Hh isoforms tagged by hemaglutanin antigen (HA) insertion carboxyl-terminal to the self-cleavage site
The activity of a morphogen depends on the mechanisms of secretion and dispersal that shape its access to cells of a receptive field
Summary
The Hedgehog (Hh) family encodes secreted morphogens with roles in patterning, stem cell maintenance and neoplastic disease (Jiang and Hui, 2008; Scales and de Sauvage, 2009; Varjosalo and Taipale, 2008). A unifying and unresolved question concerning these activities is how they are shaped by the secretion and transport mechanisms that deliver Hh to receptive cells. The interplay between apical and basal release mechanisms can be complex and interdependent (Callejo et al, 2011). It has become clear that patterning previously thought to rely on diffusion in extracellular space might instead involve actin-based cellular extensions (e.g. cytonemes) that transport Hh over many cell diameters prior to release (Rojas-Ríos et al, 2012; and reviewed in Kornberg, 2011)
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