The various hormones of the anterior pituitary are expressed in a spec
ific temporal and spatial pattern during organogenesis, which is inter
preted as a reflection of a temporal pattern of pituitary cytodifferen
tiation. The first pituitary transcripts detected are from alpha GSU,
which encodes the alpha-subunit common to the gonadotropins (FSH and L
H) and TSH. TSH beta-subunit transcripts appear several days later but
precede transcription of the GH and FSH beta and LH beta-subunit gene
s. To determine the lineage relationship between the alpha-subunit-exp
ressing cells and the other hormone-producing cells of the anterior pi
tuitary, we have employed the technique of transgene ablation. Transge
nic mice were generated that express either the normal diphtheria toxi
n A chain or a 30-fold less active attenuated version in pituitary gon
adotrope and thyrotrope cells. The absence of detectable transcripts f
or alpha-subunit, TSH beta-subunit, or LH beta-subunit by in situ hybr
idization confirmed that ablation was complete. In spite of the absenc
e of gonadotropes and thyrotropes, the GH and ACTH-producing cells dev
eloped normally. These results imply that although thyrotropes appear
early in pituitary development, they are not obligate intermediates in
the developmental pathway. Instead, commitment to individual differen
tiated pituitary cell fates must occur autonomously or before the expr
ession of currently known differentiation markers.