Abstract
Mutations in the prophet of PIT1 gene (PROP1) are the most common cause of multiple pituitary hormone deficiency in humans; however, the mechanism of PROP1 action is not well understood. We report that Prop1 is essential for dorsally restricted expression of a Groucho-related gene, transducin-like enhancer of split 3 (Tle3), which encodes a transcriptional corepressor. Deficiency of a related gene, amino terminal enhancer of split (Aes), causes pituitary anomalies and growth insufficiency. TLE3 and AES have been shown to interact with TCF/LEF (transcripiton factors of the T cell-specific and lymphoid enhancer specific group) family members in cell culture systems. In the absence of TCF4 (Tcf7L2), Prop1 levels are elevated, pituitary hyperplasia ensues and palate closure is abnormal. Thus, we demonstrate that Tcf4 and Aes influence pituitary growth and development, and place Tcf4 and Tle3 in the genetic hierarchy with Prop1.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Cell Differentiation
-
Co-Repressor Proteins / genetics
-
Co-Repressor Proteins / metabolism*
-
Gene Deletion
-
Gene Expression Regulation, Developmental*
-
Homeodomain Proteins / genetics
-
Homeodomain Proteins / metabolism*
-
Hyperplasia / genetics
-
Hyperplasia / metabolism
-
Hyperplasia / pathology
-
In Situ Hybridization
-
Mice
-
Mice, Transgenic
-
Nerve Tissue Proteins / deficiency
-
Nerve Tissue Proteins / genetics
-
Nerve Tissue Proteins / metabolism*
-
Pituitary Gland / embryology*
-
Pituitary Gland / metabolism*
-
Pituitary Gland / pathology
-
Proteins / genetics*
-
RNA, Messenger / genetics
-
RNA, Messenger / metabolism
-
TCF Transcription Factors
-
Transcription Factor 7-Like 2 Protein
-
Transcription Factors / deficiency
-
Transcription Factors / genetics
-
Transcription Factors / metabolism*
Substances
-
Co-Repressor Proteins
-
Homeodomain Proteins
-
Nerve Tissue Proteins
-
Prophet of Pit-1 protein
-
Proteins
-
RNA, Messenger
-
TCF Transcription Factors
-
TCF7L2 protein, human
-
TLE3 protein, human
-
Tcf7l2 protein, mouse
-
Tle3 protein, mouse
-
Tle5 protein, mouse
-
Transcription Factor 7-Like 2 Protein
-
Transcription Factors