Repression of Igf1 expression by Ezh2 prevents basal cell differentiation in the developing lung
Laura A Galvis, Aliaksei Z Holik, Kieran M Short, Julie Pasquet, Aaron TL Lun, Marnie E Blewitt, Ian M Smyth, Matthew E Ritchie, Marie-Liesse Asselin-Labat
DEVELOPMENT | COMPANY BIOLOGISTS LTD | Published : 2015
Epigenetic mechanisms involved in the establishment of lung epithelial cell lineage identities during development are largely unknown. Here, we explored the role of the histone methyltransferase Ezh2 during lung lineage determination. Loss of Ezh2 in the lung epithelium leads to defective lung formation and perinatal mortality. We show that Ezh2 is crucial for airway lineage specification and alveolarization. Using optical projection tomography imaging, we found that branching morphogenesis is affected in Ezh2 conditional knockout mice and the remaining bronchioles are abnormal, lacking terminally differentiated secretory club cells. Remarkably, RNA-seq analysis revealed the upregulation of ..View full abstract
Awarded by Australian National Health and Medical Research Council grant
M.-L.A.-L. and M.E.B. are supported by Australian Research Council Queen Elizabeth II Fellowships. A.T.L.L. is supported by an Elizabeth and Vernon Puzey Scholarship from the University of Melbourne. L.A.G. is supported by Strathmore Community College Scholarship. This work was supported in part by an Australian National Health and Medical Research Council grant to M.-L.A.-L., M.E.B. and M.E.R [APP1079756]. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. Deposited in PMC for immediate release.