Coordination of cell cycle and morphogenesis during organ formation

Abstract

Organ formation requires precise regulation of cell cycle and morphogenetic events. Using the Drosophila embryonic salivary gland (SG) as a model, we uncover the role of the SP1/KLF transcription factor Huckebein (Hkb) in coordinating cell cycle regulation and morphogenesis. The hkb mutant SG exhibits defects in invagination positioning and organ size due to abnormal death of SG cells. Normal SG development involves distal-to-proximal progression of endoreplication (endocycle), whereas hkb mutant SG cells undergo abnormal cell division, leading to cell death. Hkb represses the expression of key cell cycle and pro-apoptotic genes in the SG. Knockdown of cyclin E or cyclin-dependent kinase 1, or overexpression of fizzy-related rescues most of the morphogenetic defects observed in the hkb mutant SG. These results indicate that Hkb plays a critical role in controlling endoreplication by regulating the transcription of key cell cycle effectors to ensure proper organ formation.