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PITX genes are required for cell survival and Lhx3 activation.

Charles, Michael A; Suh, Hoonkyo; Hjalt, Tord LU ; Drouin, Jacques; Camper, Sally A and Gage, Philip J (2005) In Molecular Endocrinology 19(7). p.1893-1903
Abstract
The PITX family of transcription factors regulate the development of many organs. Pitx1 mutants have a mild pituitary phenotype, but Pitx2 is necessary for the development of Rathke's pouch, expression of essential transcription factors in gonadotropes, and expansion of the Pit1 lineage. We report that lack of Pitx2 causes the pouch to undergo excessive cell death, resulting in severe pituitary hypoplasia. Transgenic overexpression of PITX2 in the pituitary can increase the gonadotrope population, suggesting that the absolute concentration of PITX2 is important for normal pituitary cell lineage expansion. We show that PITX1 and PITX2 proteins are present in similar expression patterns throughout pituitary development and in the mature... (More)
The PITX family of transcription factors regulate the development of many organs. Pitx1 mutants have a mild pituitary phenotype, but Pitx2 is necessary for the development of Rathke's pouch, expression of essential transcription factors in gonadotropes, and expansion of the Pit1 lineage. We report that lack of Pitx2 causes the pouch to undergo excessive cell death, resulting in severe pituitary hypoplasia. Transgenic overexpression of PITX2 in the pituitary can increase the gonadotrope population, suggesting that the absolute concentration of PITX2 is important for normal pituitary cell lineage expansion. We show that PITX1 and PITX2 proteins are present in similar expression patterns throughout pituitary development and in the mature pituitary. Both transcription factors are preferentially expressed in adult gonadotropes and thyrotropes, suggesting the possibility of overlap in maintenance of adult pituitary functions within these cell types. Double knockouts of Pitx1 and Pitx2 exhibit severe pituitary hypoplasia and fail to express the transcription factor LHX3. This indicates that these PITX genes are upstream of Lhx3 and have compensatory roles during development. Thus, the combined dosage of these PITX family members is vital for pituitary development, and their persistent coexpression in the adult pituitary suggests a continued role in maintenance of pituitary function. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Endocrinology
volume
19
issue
7
pages
1893 - 1903
publisher
The Endocrine Society
external identifiers
  • wos:000229951500019
  • pmid:15761027
  • scopus:19444377916
ISSN
0888-8809
DOI
10.1210/me.2005-0052
language
English
LU publication?
yes
id
3b5c6f54-06bc-4009-8580-b46b8b756f1d (old id 135054)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15761027&dopt=Abstract
date added to LUP
2007-07-11 11:41:15
date last changed
2017-10-01 04:46:34
@article{3b5c6f54-06bc-4009-8580-b46b8b756f1d,
  abstract     = {The PITX family of transcription factors regulate the development of many organs. Pitx1 mutants have a mild pituitary phenotype, but Pitx2 is necessary for the development of Rathke's pouch, expression of essential transcription factors in gonadotropes, and expansion of the Pit1 lineage. We report that lack of Pitx2 causes the pouch to undergo excessive cell death, resulting in severe pituitary hypoplasia. Transgenic overexpression of PITX2 in the pituitary can increase the gonadotrope population, suggesting that the absolute concentration of PITX2 is important for normal pituitary cell lineage expansion. We show that PITX1 and PITX2 proteins are present in similar expression patterns throughout pituitary development and in the mature pituitary. Both transcription factors are preferentially expressed in adult gonadotropes and thyrotropes, suggesting the possibility of overlap in maintenance of adult pituitary functions within these cell types. Double knockouts of Pitx1 and Pitx2 exhibit severe pituitary hypoplasia and fail to express the transcription factor LHX3. This indicates that these PITX genes are upstream of Lhx3 and have compensatory roles during development. Thus, the combined dosage of these PITX family members is vital for pituitary development, and their persistent coexpression in the adult pituitary suggests a continued role in maintenance of pituitary function.},
  author       = {Charles, Michael A and Suh, Hoonkyo and Hjalt, Tord and Drouin, Jacques and Camper, Sally A and Gage, Philip J},
  issn         = {0888-8809},
  language     = {eng},
  number       = {7},
  pages        = {1893--1903},
  publisher    = {The Endocrine Society},
  series       = {Molecular Endocrinology},
  title        = {PITX genes are required for cell survival and Lhx3 activation.},
  url          = {http://dx.doi.org/10.1210/me.2005-0052},
  volume       = {19},
  year         = {2005},
}