Coordination of cell cycle and morphogenesis during organ formation.

Abstract

Organ formation requires precise regulation of cell cycle and morphogenetic events. Using the <i>Drosophila</i> 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 <i>hkb</i> mutant SG exhibits defects in invagination positioning and organ size due to the abnormal death of SG cells. Normal SG development involves distal-to-proximal progression of endoreplication (endocycle), whereas <i>hkb</i> 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 <i>cyclin E</i> or <i>cyclin-dependent kinase 1,</i> or overexpression of <i>fizzy-related</i> rescues most of the morphogenetic defects observed in the <i>hkb</i> 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.