The migration of limb myogenic precursors from limb level somites to their 
ultimate site of differentiation in the limb is a paradigmatic example of a set 
of dynamic and orchestrated migratory cell behaviours. The homeobox containing 
transcription factor ladybird homeobox 1 (Lbx1) is a central regulator of limb 
myoblast migration, null mutations of Lbx1 result in severe disruptions to limb 
muscle formation, particularly in the distal region of the limb in mice (Gross 
et al., 2000). As such Lbx1 has been hypothesized to control lateral migration 
of myoblasts into the distal limb anlage. It acts as a core regulator of the 
limb myoblast migration machinery, controlled by Pax3. A secondary role for Lbx1 
in the differentiation and commitment of limb musculature has also been proposed 
(Brohmann et al., 2000; Uchiyama et al., 2000). Here we show that lateral 
migration, but not differentiation or commitment of limb myoblasts, is 
controlled by the phosphorylation of three adjacent serine residues of LBX1. 
Electroporation of limb level somites in the chick embryo with a 
dephosphomimetic form of Lbx1 results in a specific defect in the lateral 
migration of limb myoblasts. Although the initial delamination and migration of 
myoblasts is unaffected, migration into the distal limb bud is severely 
disrupted. Interestingly, myoblasts undergo normal differentiation independent 
of their migratory status, suggesting that the differentiation potential of 
hypaxial muscle is not regulated by the phosphorylation state of LBX1. 
Furthermore, we show that FGF8 and ERK mediated signal transduction, both 
critical regulators of the developing limb bud, have the capacity to induce the 
phosphorylation of LBX1 at these residues. Overall, this suggests a mechanism 
whereby the phosphorylation of LBX1, potentially through FGF8 and ERK 
signalling, controls the lateral migration of myoblasts into the distal limb 
bud.