The diverse cellular contributions to the skeletal elements of the vertebrate 
shoulder and pelvic girdles during embryonic development complicate the study of 
their patterning. Research in avian embryos has recently clarified part of the 
embryological basis of shoulder formation. Although dermomyotomal cells provide 
the progenitors of the scapular blade, local signals appear to have an essential 
guiding role in this process. These signals differ from those that are known to 
pattern the more distal appendicular skeleton. We have studied the impact of 
Tbx15, Gli3, Alx4 and related genes on formation of the skeletal elements of the 
mouse shoulder and pelvic girdles. We observed severe reduction of the scapula 
in double and triple mutants of these genes. Analyses of a range of complex 
genotypes revealed aspects of their genetic relationship, as well as functions 
that had been previously masked due to functional redundancy. Tbx15 and Gli3 
appear to have synergistic functions in formation of the scapular blade. 
Scapular truncation in triple mutants of Tbx15, Alx4 and Cart1 indicates 
essential functions for Alx4 and Cart1 in the anterior part of the scapula, as 
opposed to Gli3 function being linked to the posterior part. Especially in 
Alx4/Cart1 mutants, the expression of markers such as Pax1, Pax3 and Scleraxis 
is altered prior to stages when anatomical aberrations are visible in the 
shoulder region. This suggests a disorganization of the proximal limb bud and 
adjacent flank mesoderm, and is likely to reflect the disruption of a mechanism 
providing positional cues to guide progenitor cells to their destination in the 
pectoral girdle.