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Status |
Public on Feb 26, 2020 |
Title |
PROP1-Dependent Retinoic Acid Signaling Regulates Developmental Pituitary Morphogenesis and Hormone Expression |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Dietary vitamin A is metabolized into bioactive retinoic acid in vivo and regulates the development of many embryonic tissues. Retinoic acid signaling is active in the oral ectoderm-derived tissues of the neuroendocrine system, but its role there has not yet been fully explored. We show here that retinoic acid signaling is active during pituitary organogenesis and dependent on the pituitary transcription factor Prop1. Prop1-mutant mice show reduced expression of the aldehyde dehydrogenase gene Aldh1a2, which metabolizes the vitamin A-intermediate retinaldehyde into retinoic acid. In order to elucidate the specific function of RA signaling during neuroendocrine development, we studied a conditional deletion of Aldh1a2 and a dominant-negative mouse model of inhibited retinoic acid signaling during pituitary organogenesis. These models partially phenocopy Prop1-mutant mice by exhibiting embryonic pituitary dysmorphology and reduced hormone expression, especially of thyroid-stimulating hormone. These findings establish the critical role of retinoic acid in embryonic pituitary stem cell progression to differentiated hormone cells and raise the question of gene-by-environment interactions as contributors to pituitary development and disease.
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Overall design |
10x Chromium single-cell RNA sequencing data of pituitary cells from one P4 female Hesx1Cre/+ and one P4 female Hesx1Cre/+; R26dnRAR/dnRAR mouse
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Contributor(s) |
Cheung LY, Camper SA |
Citation(s) |
31913463 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
R01 HD030428 |
A Panhypopituitary Mouse Mutation |
REGENTS OF THE UNIVERSITY OF MICHIGAN - ANN ARBOR |
Sally A. Camper |
R01 HD034283 |
Cell specific expression in the pituitary gland |
REGENTS OF THE UNIVERSITY OF MICHIGAN - ANN ARBOR |
Sally A. Camper |
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Submission date |
Dec 16, 2019 |
Last update date |
Feb 26, 2020 |
Contact name |
Leonard YM Cheung |
E-mail(s) |
leonard.cheung@stonybrook.edu
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Phone |
6312162617
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Organization name |
Stony Brook University
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Street address |
101 Nicolls Road
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City |
Stony Brook |
State/province |
New York |
ZIP/Postal code |
11794 |
Country |
USA |
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Platforms (1) |
GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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Samples (2) |
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Relations |
BioProject |
PRJNA595868 |
SRA |
SRP237752 |