Cell Cycle Dependent Mechanisms Governing Tissue Morphogenesis

Tissue morphogenesis is a process that contributes to building organs as well as orchestrating embryogenesis. In diseases such as cancer and congenital malformation, biological tissues fail to build or maintain a correct, non-diseased multicellular pattern. Therefore, an important open-ended question is what mechanisms hold cells together and shape them into functional structures? In many cases, de novo lumen formation from cells that transition from non-polarized to polarized is an important driver of tissue morphogenesis. One example of this is the assembly of a Left-Right Organizer (LRO) (Amack and Yost, 2004). The LRO is required to place visceral and abdominal organs with respect to left-right body axes (Kimelman and Martin, 2011). Due to the conservation of the LRO, we will utilize zebrafish, to understand the role of cell division during its formation. Our studies examining LRO formation identify that epithelialization and de novo lumen formation occur through a sequential process that starts with cell division and placement of the cytokinetic bridge/midbody. Our in vivo analysis suggests that the cytokinetic bridges provides mechanical coupling, allowing cells to pack into biologically useful, yet energetically unfavorable states where they develop into epithelial cells and form a centralized lumen.