Anterior pituitary cells defective in the cell-autonomous factor, df, undergo cell lineage specification but not expansion.
The Ames dwarf mouse transmits a recessive mutation (df) resulting in a profound anterior pituitary hypocellularity due to a general lack of thyrotropes, somatotropes and lactotropes. These cell types are also dependent on the pituitary-specific transcription factor, Pit-1. We present evidence that expression of Pit-1 and limited commitment to these cells lineages occurs in df/df pituitaries. Thus, the crucial role of df may be in lineage-specific proliferation, rather than cytodifferentiation. The presence of all three Pit-1-dependent cell types in clonally derived clusters provides compelling evidence that these three lineages share a common, pluripotent precursor cell. Clusters containing different combinations of Pit-1-dependent cell types suggests that the Pit-1+ precursor cells choose from multiple developmental options during ontogeny. Characterization of df/df<-->+/+ chimeric mice demonstrated that df functions by a cell-autonomous mechanism. Therefore, df and Pit-1 are both cell-autonomous factors required for thyrotrope, somatotrope and lactotrope ontogeny, but their relative roles are different.
Gage
P J
PJ
Department of Human Genetics, University of Michigan Medical School, Medical Science II M3816, Ann Arbor 48109-0618, USA.
Roller
M L
ML
Saunders
T L
TL
Scarlett
L M
LM
Camper
S A
SA
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002678:Chimera; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004392:Dwarfism / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D005260:Female; D013006:Growth Hormone / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010903:Pituitary Gland, Anterior / Q000002:abnormalities* / Q000166:cytology* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D017931:DNA Primers; D004268:DNA-Binding Proteins; D013006:Growth Hormone; D011388:Prolactin; D013972:Thyrotropin; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; C494185:Pou1f1 protein, mouse