The spleen is a vertebrate organ that has both hematopoietic and immunologi
c function. The embryonic origins of the spleen are obscure, with most stud
ies describing the earliest rudiment of the spleen as a condensation of mes
odermal mesenchyme on the left side of the dorsal mesogastrium, The develop
ment of spleen handedness has not been described previously, presumably bec
ause of the difficulty in assaying spleen position in the embryo and the la
ck of early, organ-specific molecular markers. Here we show that expression
of the homeobox gene Nkx2-5 serves as a marker for spleen precursor tissue
. Pre-splenic tissue is initially located in symmetric domains on both side
s of the embryo but, during subsequent development, only the left side goes
on to form the mature spleen. Therefore, the final location of the spleen
on the left side of the body a,axis appears to result from preferential dev
elopment of the spleen precursor cells on the left side of the embryo. Our
studies indicate that the spleen and heart become asymmetric via different
cellular mechanisms, Nkx2-5 may function locally as part of the laterality
cascade, downstream of nodal and Pitx2, or it may direct asymmetric morphog
enesis after laterality has been determined.