Cellular Mechanisms Underlying Formation and Elongation of Axial Structures in Mouse Embryos

Williams, Margot Lillian Kossmann, Department of Cell Biology, University of Virginia
Sutherland, Ann, Department of Cell Biology, University of Virginia
Lu, Xiaowei, Department of Cell Biology, University of Virginia
Desimone, Douglas, Department of Cell Biology, University of Virginia
Keller, Ray, Department of Biology, University of Virginia

All vertebrate embryos, which generally begin as a sphere or disc, must form an elongated body axis with a head on one end and a tail on the other. Defects in axial elongation result not only in a shortened body axis, but are also often associated with neural tube closure defects. Cell behaviors contributing to the elongation of axial structures are well understood in anamniote model systems, but are only now being elucidated in mammalian embryos. Through the development of novel culturing and imaging techniques, we are able to directly observe murine development by live timelapse confocal imaging. Using this four-dimensional imaging approach, we have identified cellular mechanisms underlying the formation and elongation of several axial structures within mouse embryos, including the primitive streak, neural plate, and notochordal plate. We have found that, unlike its avian counterpart, the murine primitive streak does not form through convergent extension (CE), but rather by progressive initiation of epithelial-mesenchymal transition (EMT). The neural plate undergoes CE by mediolateral cell intercalation, a process which includes cooperation of distinct apical and basolateral mechanisms within neural epithelial cells, and is under the control of planar cell polarity (PCP) signaling. Finally, the notochordal plate also exhibits mediolateral cell intercalation, which occurs concomitantly with directed lamellipodia-driven migration. Some of these cellular mechanisms are strikingly similar to, and others surprisingly different from, those at work in other model systems. These findings greatly increase our understanding of mammalian development, and have important implications in the evolution of developmental processes.

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PHD (Doctor of Philosophy)
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