Primary cilia and BBS4 are required for postnatal pituitary development.

Primary cilia orchestrate several signaling pathways, and their disruption results in pleiotropic disorders called ciliopathies. Bardet-Beidl syndrome (BBS), one ciliopathy, provides insights into cilia function in many tissues. Using a mouse model of BBS, Bbs4 knockout (Bbs4(-/-)), we found that adult Bbs4(-/-) pituitaries are hypoplastic and have increased gonadotroph populations. Similarly, pituitary deletion of IFT88, required for ciliogenesis, attenuated growth and increased gonadotrophs. The developing Bbs4(-/-) pituitary experienced mildly reduced Hedgehog (HH) signaling. Isolated Bbs4(-/-) pituitary stem cells exhibited reduced HH signal responsiveness and expression of stem cell markers. These data demonstrate that cilia and BBS function are necessary for pituitary growth. We propose that altered cilia-mediated patterning of the pituitary contribute to physiological features of ciliopathies such as BBS.