International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


14:30 – 14:45 HRS


Camper SA
University of Michigan, USA

Co-Authors: 1) Brinkmeier ML, 2) Carninci P, 1) Lyons RH, 2) Shiraki T, 2) Arakawa T, 2) Kawai J, 2) Hayashizaki Y
Institutions: 1) University of Michigan, USA. 2) RIKEN Genomic Sciences Center, Japan

Prop1 encodes a paired-like homeodomain transcription factor necessary for normal pituitary growth, shape, and cell specification. It is expressed only in embryonic pituitary, peaking at e12.5. PROP1 mutations are the most common cause of multiple pituitary hormone deficiency in humans, but few transcriptional targets are known. We employed three gene discovery approaches to identify Prop1 targets and novel factors influencing pituitary development. Differential display and subtractive hybridization methods applied to RNA prepared from dissected embryonic pituitary primordia proved to be a rich source of novel genes. Several members of the Wnt signaling pathway were represented, and two, Tcf7l2 and Aes, were confirmed to have functional roles in pituitary growth and shape. The value of these libraries is limited by the short cDNAs typically produced. We prepared three full length cDNA libraries from pituitary primordia of normal (e12.5, e14.5) and mutant (e14.5) embryos using the cap-trapper method. Our libraries were among the best of the Riken encyclopedia for novel gene discovery. Of 32,476 clones sequenced, about 20% were previously unknown. The pituitary cDNAs hit 18 molecular function Gene Ontology categories, with the most in binding (46%) and enzyme (31%). There were 707 DNA binding transcription factor hits. These cDNA libraries are a valuable resource for understanding the mechanism of Prop1 action, and we expect they will facilitate elucidation of the underlying cause of additional pituitary genetic diseases in humans.

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