Biomedical Engineering Reference
In-Depth Information
Figure 8.7.
The trajectory described by the tip of nodal monocilia is elliptic with
the axis of rotation tilted toward the posterior side. The larger the distance between
tip and nodal surface, the stronger the fluid layer is pushed into the direction of
ciliar motion. The ciliar motion thus gives rise to a fast flow just above the tip from
right to left, and to a backward flow close to the nodal surface from left to right.
The backward flow is much slower due to the viscous resistance of the wall. Figure
is reprinted from [13]. Copyright (2006), with permission from Elsevier. (See color
insert.)
the flow (by initiating a calcium-dependent signal transduction event) [65, 66]. In
both approaches the cilia-generated flow plays an essential role which triggers the
symmetry-breaking event.
Stimulation models were introduced to explain the observed differences in the
lateral expression patterns between mutant embryos lacking nodal cilia and mu-
tants with only immotile cilia [11]. Here, we will only discuss the chemical-gradient
models. The cilia-generated flow transports morphogens secreted into the cavity of
the ventral node leading to an accumulation on the left side. For suciently large
morphogenic proteins, the nodal flow is fast enough to generate a concentration
gradient with a higher concentration on the left side. However, for smaller proteins
this gradient might be destabilized by the rightward backflow discussed earlier. To
circumvent these diculties, Hirokawa and coworkers have suggested that vesicles
might carry the morphogens which release them by rupturing on the left side [67].
However, the precise rupturing mechanism remains unclear.
Generally, it is believed that morphogens are detected by receptors placed on
both the left and right side of the node. However, the concentration gradient then
leads to asymmetric signaling transduction events. The precise mechanisms are not
known. An overview of currently discussed reaction-diffusion models can be found
in [54, 68].
Finally, it should be emphasized that despite considerable progress in the under-
standing of this system, some key questions remain unanswered: What makes the
flow leftward, i.e., what is the origin of the asymmetry in cilia? Is the establishment
of the nodal flow the initial L-R symmetry-breaking event in vertebrates? And, how
universal is this mechanism in vertebrates?
8.4.2 Theoretical Modeling
One of the main theoretical challenges is to show that the nodal flow can stabilize a
morphogen concentration gradient. This question has been addressed by Cartwright
