Diaphragms from Fog2 lil mice show an intact membrane with a defect in muscular patterning (see Figure 1B). The membranous portion of the diaphragm is populated by a migratory population of muscle precursor cells, much like the limbs [19,20]. Mice with defects in genes known to be important for the control of this process have intact but amuscular diaphragms [17,21,22]. Hepatocyte growth factor/Scatter factor (HGF) is one potential candidate responsible for the guidance of muscle precursors to the membranous diaphragm. It has been shown that HGF is expressed along this anatomic pathway [23], and mice with absence of the HGF receptor c-Met fail to form muscularized pleuroperitoneal folds (PPFs), and thus have amuscular diaphragms [24,25]. Fog2 is expressed diffusely in the early amuscular diaphragm at E11.5 as well as in the later muscularized diaphragm (see Figure 3C and 3D). Pax3 and MyoD, transcription factors required for appropriate migration and determination of myogenic precursors, were detected in the PPFs of Fog2 lil mice (data not shown). However, in situ expression analysis demonstrated that the expression of HGF in the region where this structure meets the membranous diaphragm was markedly reduced in Fog2 mutant mice (Figure 6). We hypothesize that Fog2 is required (either directly or indirectly) for the induction of HGF in the developing diaphragm, and dysregulation of HGF patterning along the path of muscle precursor cell migration between the PPF and the diaphragm accounts for the abnormal phenotype in these mice.