Normal mammary development and function in mice with Ift88 deleted in MMTV- and K14-Cre expressing cells

Area of Science:

• Cell Biology
• Developmental Biology
• Organelle Function

Background:

• Primary cilia (PC) are microtubule-based organelles vital for embryonic and postnatal development.
• PC regulate critical signaling pathways, including the Hedgehog (Hh) pathway, impacting mammary gland development and stem/progenitor cell populations.

Purpose of the Study:

• To investigate the role of PC in mammary gland development and stem/progenitor cell function.
• To determine the necessity of PC in luminal epithelial, basal epithelial, and stromal cells of the mammary gland.

Main Methods:

• Generated mouse models with PC deletion in specific mammary cell types using MMTV-Cre, K14-Cre, and Prx1-Cre.
• Utilized ROSA26 reporters to confirm Cre activity and immunofluorescence to verify PC disruption.
• Enriched mammary stem and progenitor cells via mammosphere culture and deleted Ift88 to assess PC function.

Main Results:

• Prx1-Cre; Ift88Del mice showed pubertal defects in terminal end buds, but this was not intrinsic to the mammary gland.
• No significant alterations in mammary development or function were observed in MMTV-Cre or K14-Cre; Ift88Del mice.
• PC were highly expressed on mammary stem and progenitor cells; their depletion reduced primary mammosphere formation but not secondary mammosphere outgrowth.

Conclusions:

• Primary cilia regulate systemic factors influencing early pubertal mammary development.
• PC in MMTV- or K14-expressing epithelial cells are dispensable for normal mammary development and function.
• PC are essential for establishing mammospheres in culture, but not for their subsequent renewal.