Muscle founder cells regulate defasciculation and targeting of motor axonsin the Drosophila embryo

During Drosophila embryogenesis, motor axons leave the central nervous syst em (CNS) as two separate bundles, the segmental nerve (SN) and intersegment al nerve (ISN), From these, axons separate (defasciculate) progressively in a characteristic pattern, initially as nerve branches and then as individu al axons, to innervate target muscles [1,2], This pattern of branching rese mbles the outgrowth and defasciculation of motor axons from the neural tube of vertebrate embryos, The factors that trigger nerve branching are unknow n, In vertebrate limbs, the branched innervation may depend on mesodermal c ues, in particular on the connective tissues that organise the muscle patte rn [3]. In Drosophila, the muscle pattern is organised by specific mesoderm al cells, the founder myoblasts, which initiate the development of individu al muscles [4-6], Founder myoblasts fuse with neighbouring non-founder myob lasts and entrain these to a specific muscle programme, which also determin es their innervation [4,7], In the absence of mesoderm, ISN and SN can form , but motor axons fail to defasciculate from these bundles [7], The cue(s) for nerve branching therefore lie within the mesoderm, most likely in the m uscles and/or in the precursor cells of the adult musculature [8], Here, we show that founder myoblasts are the source of the cue(s) that are required to trigger defasciculation and targeted growth of motor axons. Moreover, w e found that a single founder myoblast can trigger the defasciculation of a n entire nerve branch. This suggests that the muscle field is structured in to sets of muscles, each expressing a common defasciculation cue for a part icular nerve branch.