Identification of genes expressed during pituitary gland organogenesis.

Abstract

The anlage of the pituitary gland begins to develop at embryonic day 9.0 (e9.0) in response to inductive signals provided by surrounding tissues. Signals from the ventral diencephalon and juxtaposed mesenchymal cells induce spatially restricted patterns of transcription factor expression in the nascent pituitary. These stratified transcription factor domains are translated into distinct regions of cell differentiation within the gland. Several critical genes regulating pituitary gland development have been identified previously through the characterization of hereditary pituitary defects in mice and humans. Pituitary transcription factors such as <italic>Pitx2, Lhx3, Hesx1</italic>, and <italic>Prop1</italic> are essential for pituitary gland development, however their downstream targets remain largely unknown. To gain a better understanding of the molecular events regulating pituitary gland development, a partial transcriptome of the developing organ was generated using differential display and cDNA subtractive hybridization. Developmentally regulated pituitary transcripts expressed at e12.5 and e14.5 were compared through differential display, and PROP1-dependent transcripts expressed at e14.5 were identified using cDNA subtractive hybridization. A total of 485 expressed sequence tags (ESTs) were identified in these analyses. Fifty-four percent represent known genes, 39% have sequence similarity to previously identified ESTs from other tissues, and 6% represent novel sequences. Of a small subset tested, four transcripts were proven to be differentially expressed. Seven clones analyzed have specific patterns of expression within anterior lobe cell types and may represent novel markers of cell fate within the developing pituitary gland. Additionally, numerous members of the Wg/Wnt signaling pathway were identified, including the mouse ortholog of the <italic>frizzled 2</italic> receptor and a novel isoform of the <italic>Tcf712</italic> transcription factor. Some of the transcripts identified in this study are likely to be important regulators of pituitary gland development and disease.