Biomedical Engineering Reference
In-Depth Information
Figure 8.6.
In KIF3b
−
-mutants (which lack KIF3B, kinesin superfamily proteins)
nodal monocilia are absent and left-right asymmetry is not established. While in
the wildtype (left side A) the cilia-generated flow over the node leads to a directed
placement of organs, their location is completely random in the mutant (right side
B). If mutants are subjected to an artificial external flow (having the same direction
as the nodal flow) left-right patterning is, however, re-established [62]. Figure is
reprinted from [11]. Copyright (1998), with permission from Elsevier.
leftward flow. As shown by Okada et al. in [56] nearly 20% of all cilia are anteriorly
tilted in
inv
mutants. For these monocilia the “power stroke” occurs during their
rightward motion, while the leftward occurs close to the wall. Also around 20% of the
cilia exhibit a counterclockwise rotation. This disordered arrangement of rotational
vector gives rise to the typical “meandering” flow observed in [54]. In
iv
mutants,
the monocilia appeared to be very rigid. They hardly moved and apparently were
frozen [54].
Thus, there is strong experimental evidence that monocilia generate the nodal
flow from right to left. However, so far it is not clear by which mechanism the ciliar
flow influences the vertebrate development. More specifically, how is the movement
of fluid across the node translated into asymmetric patterns of gene expression?
Currently, several models are being discussed that speculate on the physiological
role of the nodal flow: i) models in which the nodal flow leads to the formation of
concentration gradients of secreted morphogens (such as Fgf8, GDF1, and Nodal)
[11, 56]; and ii) stimulation models with two different kind of cilia. Here it is assumed
that only some of the nodal cilia are motile. The remaining cilia act as sensors of
