Universiteit Leiden

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Dissertation

A time-space translation mechanism for patterning the vertebrate anteroposterior axis

My PhD project studies how the temporally sequential Hox gene expression is regulated during head-tail patterning of the frog embryo.

Author
K. Zhu
Date
29 November 2017
Links
Thesis in Leiden Repository

My PhD project studies how the temporally sequential Hox gene expression is regulated during head-tail patterning of the frog embryo. This question has not been solved and remains one of the greatest unsolved mysteries in developmental biology. Currently, a very attractive explanation attributes sequential Hox gene activation to progressive opening of the chromosome, because it parallels the linear arrangement of Hox genes on the chromosome. While promising, this explanation is surrounded by extra complexities that ensure Hox expression is synchronized between different cells. By using gain-of-function and loss-of-function approaches, I discovered that Hox-Hox interactions play a crucial role in the regulation of Hox expression, and for the first time, I dissected different roles for these interactions in axis formation. The findings are likely to resolve the above complexities, and reveal a new facet of the mechanisms underlying Hox gene regulation. Furthermore, by timed modulation of the actions of BMP signaling, I showed that there is a BMP-dependent timing mechanism in the head that could be continued by the Hox temporal sequence in the trunk. The two constitute an integrative timer which can be translated into spatial patterns of gene expression along the whole head-tail axis via a BMP/anti-BMP dependent mechanism.