Functional analysis of Protocadherin18a in zebrafish early development

“It is not birth, marriage, or death, but gastrulation, which is truly the most important
time in your life.” (Lewis Wolpert, 1986).
Gastrulation is a pivotal phase of early embryonic development and leads to the
formation of the defining axial structure of all Chordates: the notochord. It is
essentially the result of major cell rearrangements and is driven by the coordinated
movement of mesodermal cells, often referred to as collective cell migration.
Cohesion is guided by various factors and stays connected via cadherin-based
junctions. In recent years, significant interest has been focused on the largest group
within the cadherins superfamily, the protocadherins. The presence of protocadherins
in the nervous system has commanded the most attention while little is known about
their role in cell-cell adhesions in early development.
In this work, I defined the role of Pcdh18a, a novel member of protocadherins in
zebrafish gastrulation. Pcdh18a is expressed in a confined cell group – termed the
notochord tip cells and exhibit strong connection to the trailing notochord progenitors.
At the molecular level, Pcdh18a mediates the recycling of E-cadherin and thereby
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affects the migratory capabilities of cells. Using the Cellular Potts model, we were
able to simulate the migration of mesodermal cells in early zebrafish development.
Our model predicted that high motility and strong adhesiveness of Pcdh18a-positive
prechordal plate is a prerequisite of proper axis formation during gastrulation.