Figure 7
Summary of the signaling modalities characterizing each of the functions of HGF/Met in MNs. (A,B) Schematic summary of the MN populations in which HGF exerts its functions, highlighting which subsets express Met. (A) Scheme representing the three subsets of Pea3-expressing MNs, and the mechanism by which GDNF and HGF cooperate to establish Pea3 expression domain, based on [16]: GDNF acts on Ret/GFRa1 expressing “pioneer” neurons (dark blue pool, believed to largely match the CM MN pool in general) , to induce Pea3 expression. Pea3 in turn is required to induce expression of the HGF receptor Met. HGF acts on the same “pioneer” neurons, once they express Met, to trigger the production by these neurons of a signal (referred to as X) that induces Pea3 expression in additional neurons (“recruited”). This leads to the lateral enlargement of the CM pool (within which Met expression propagates as well), and to the recruitment of more anterior neurons (red, largely matching the LD MN pool), which will not express Met. (B) Scheme representing lumbar axonal MN projections in the hindlimb, with colours distinguishing Met-dependent from Met-independent guidance. (C) Summary table of the various biological aspects of neuromuscular development involving HGF/Met. Columns distinguish the nature of the biological response (cell fate specification, axon growth/guidance, and survival); rows distinguish the MN populations, matching them to their position in the schemes in (A, top) and (B, bottom). The table indicates for each response/MN population the respective degree of muscle dependency, the corresponding function of HGF/Met, whether it is cell autonomous or not, and the degree of execution by signalling solicited by Met2P and Met2S specificity-switch mutants (with green indicating complete execution, and red indicating abrogation).