Primary cilia and BBS4 are required for postnatal pituitary development.

This study used mice to investigate how Bardet-Biedl Syndrome affects the pituitary gland, which is a small but important gland in the brain that produces hormones controlling growth, reproduction, and other body functions. The researchers compared normal mice to mice missing the BBS4 gene (which causes one form of BBS) and found that the pituitary glands in BBS mice were smaller than normal and had an imbalance in the types of hormone-producing cells. The scientists discovered that tiny hair-like structures called cilia (which are affected in BBS) are essential for proper pituitary development after birth. When these cilia don't work correctly, important cellular communication pathways are disrupted, leading to abnormal pituitary growth and development. The stem cells that help build the pituitary also showed problems responding to growth signals. This is early-stage laboratory research using mice, but it helps explain why people with BBS often have hormone-related problems like delayed puberty or growth issues. Understanding how BBS affects pituitary development could eventually lead to better treatments for managing these hormone problems in BBS patients, though much more research would be needed to develop actual therapies.

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.