Retinoic acid signalling is a candidate regulator of the expression of pituitary-specific transcription factor Prop1...

Development of the anterior pituitary proceeds via spatiotemporal patterning of transcription factors and signalling molecules. Among them, retinoic acid (RA) functions as an important signalling molecule for vertebrate organogenesis in many tissues. However, little is known regarding the target genes in the developing pituitary. The present study aimed to clarify the relationship between endogenous RA signalling and mRNA expression of the pituitary-specific transcription factor Prop1 in the pituitary primordium of Rathke's pouch. Gene expression analysis and in situ hybridisation demonstrated that retinaldehyde dehydrogenases (Raldhs) and all types of RA receptors (Rars) are expressed at the level of transcription in the rat Rathke's pouch. Ex vivo organ culture using Rathke's pouch and an in vitro reporter assay demonstrated that RA signalling increases the expression level of Prop1 via RARα. Moreover, a reporter assay using serial truncated constructs of the 5'-upstream region of mouse Prop1 revealed a predicted cis-regulatory element of RARα. This is the first report of a relationship between RA signalling and Prop1-expression during early pituitary development.