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Title: REGULATORY AND CODING SEQUENCES OF THE PITUITARY-SPECIFIC TRANSCRIPTION FACTOR, PROP1 ARE EVOLUTIONARILY AND FUNCTIONALLY CONSERVED

Author
item CAMPER, SALLY - UNIV MICHIGAN MED SCH
item WARD, ROBERT - UNIV MICHIGAN MED SCH
item CHO, MIN CHUL - UNIV MICHIGAN MED SCH
item RAETZMAN, LORI - UNIV MICHIGAN MED SCH
item ESPOSITO, CONNIE - UNIV MICHIGAN MED SCH
item RUBIN, EDWARD - DOE JOINT GENOME INST
item Smith, Timothy - Tim
item RHODES, SIMON - INDIANA UNIV
item LYONS, ROBERT - UNIV MICHIGAN MED SCH

Submitted to: Mouse Genome Conference
Publication Type: Abstract Only
Publication Acceptance Date: 9/1/2004
Publication Date: 10/18/2004
Citation: Camper, S.A., Ward, R.D., Cho, M., Raetzman, L.T., Esposito, C., Rubin, E.M., Smith, T.P., Rhodes, S.J., Lyons, R.H. Regulatory and coding sequences of the pituitary-specific transcription factor, PROP1 are evolutionarily and functionally conserved. Proc., 18th Int. Mouse Genome Conference, Seattle, WA, 10/18-21/2004. Abstract.

Interpretive Summary:

Technical Abstract: All vertebrates have pituitary glands composed of specialized hormone-producing cells. The individual hormones are evolutionarily conserved, although their function varies across the classes on Animalia. For example, prolactin influences libido, maternal behavior and lactation in mammals, while it regulates the fish response to salinity, and it facilitates learning territorial bird songs. Even prochordates such as Ciona savignyi have pituitary-like hormones that function in regulation of growth and gonadotropin production, suggesting that the genes regulating pituitary organogenesis may be conserved throughout the phylum Chordata. The first known pituitary-specific gene in the genetic hierarchy is Prop1, a paired-like homeodomain transcription factor. PROP1 mutation are the most common known cause the multiple pituitary hormone deficiency in humans, and mice homozygous for either the spontaneous Ames dwarf mutation or the targeted null allele are good models for the human disease. We determined the sequence of the PROP1 gene in five primates, including human, gorilla, baboon, howler monkey and lemur, and compared them with the sequences of PROP1 in other orders of mammals including species representing Rodentia, Carnivora, and Artiodactyla, as well as distantly related vertebrates such as Fugu, zebrafish and chicken. A phylogenetic analysis using parsimony supported the orthologouos nature of the sequences, and suggested that PROP1 is an orphan class of paired homeodomain transcription factors. Alignment of large regions of genomic sequence from four species and VISTA analysis revealed the presence of four highly conserved noncoding sequences (CNS) in the PROP1 gene. Studies in transgenic mice confirm that CNS1 is functionally important; it confers a dorsalized expression pattern in the developing pituitary gland. Phylogenetic footprinting of CNS1 across several species implicates specific DNA binding sites in regulation of PROP1 express. In conclusion, evolutionary comparison has proven to be a valuable approach to understanding regulation of PROP1, the key gene for pituitary organ development in vertebrates.