January 13, 2009 | David F. Coppedge

Biology Now Includes Fluid Dynamic Construction

There’s an old legend that Tibetan monks built a wall by levitating heavy stones with sound by beating their drums and gongs.  Something not quite so fantastic but still amazing is done by cells in the embryo.  Scientists have filmed zebrafish embryos using beating cilia to build little stone structures that they use for balance.
    Animals need to know which way is up.  All vertebrates have pieces of rock in their heads for this purpose (see 10/10/2003).  These rocks made of calcium carbonate, called otoliths in fish and otoconia in humans, are tied to sensory organs that measure their inertia to determine balance, direction and motion.  They are interesting examples of biomineralization – the use of mineral construction materials instead of proteins, sugars, fats and nucleic acids.  Because minerals are hard things, they need to be guided into place like building blocks.  How does a little fish embryo place the building blocks for otoliths that will work?  “Otolith number, size and placement are under strict developmental control,” wrote a team of UCLA and Caltech scientists in Nature.1
    Until now it was unknown how the embryo guided the building blocks into place.  The team used high-speed digital video cameras on a microscope to film the growth of otic vesicles, the organs where otoliths form.  At 100 to 330 frames per second, they observed that cilia attracted precursor particles by beating back and forth, creating little vortices in the fluid.  At polar ends of the otic vesicles, longer cilia called “tether cilia” beat this way and attracted particles to their tips.  The beating not only set up a fluid dynamic system that pulled the particles in, it also kept the growing structure rotating for even construction.  They called this a “cilium-dependent hydrodynamic system.”
    The cilium uses dynein for motion and is dependent on a gene called Gas8 for regulation.  Here’s the jargon:

Our results demonstrate that Gas8 is required for normal motility of cilia in the otic vesicle and that ciliary motility is essential for normal ear development.  The otic vesicle is a closed epithelial organ and fluid flow within this vesicle has been suggested to contribute to otolith formation.  Our study provides direct experimental evidence in support of this hypothesis.  On the basis of high-speed video microscopy of cilia motility and quantitative analysis of precursor particle movements in wild-type and gas8 morphant embryos, we propose a new, cilium-dependent hydrodynamic mechanism for otolith biogenesis (Fig. 4).  In this model, motility of tether cilia at the poles of the otic vesicle establishes a vortex that attracts otolith precursors (Fig. 4i, l), thereby biasing an otherwise random distribution of precursor particles and concentrating them near the two patches of tether cilia.  This ensures preferential otolith seeding at the poles of the otic vesicle.  At the otic vesicle poles, tether cilia motility further serves to disperse precursor particles locally and oscillation of the otolith increases effective contact area with precursors (Fig. 4j). Together, this prevents particles from sedimenting to form ectopic aggregates and promotes efficient uniform otolith growth.

Cool.  The little fish embryo uses this organ to keep itself right-side up as it swims away.  Although the scientists observed this phenomenon in fish, they believe the mechanism may have more general application.  “Our findings add to a growing list of developmental processes requiring fluid dynamic inputs for proper growth and patterning, further showing that epigenetic cues are part of the embryonic developmental program.”  They encouraged other biologists to look for answers to hearing loss and balance problems in humans in “ciliopathies” – diseases of the cilia.
    The Supplementary Information page contains Quicktime movies where you can see the beating tether cilia with otoliths growing at their tips.2 

1.  Colantonio et al, “The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear,” Nature 457, 205-209 (8 January 2009) | doi:10.1038/nature07520.
2.  Supplementary Information page for Colantonio et al, Nature.

Think how many systems must interact in this amazing process.  Cilia are among the “irreducibly complex” organelles Michael Behe described in detail in Darwin’s Black Box and The Edge of Evolution.  All the parts of the cilia must be coded in the DNA – along with the assembly instructions for the cilia and the molecular trucks that build them (visit 06/14/2004 to be blown away by that fact).  The cilia have to find their ways to the poles of the otic vesicle.  They have to know how fast to beat to set up the proper vortex that will attract precursor particles.  They have to start and stop beating at the right time and somehow “know” when the otoliths are the right size and shape.  The sensory apparatus has to know what to do with the information provided by the inertia of the otoliths.  The brain has to process this information and send course corrections to the muscles.  A multitude of ancillary proteins, hormones and regulatory factors are involved.  This is just for one sense organ in a tiny fish embryo.  Did the fish figure this all out by trial and error?  Remember – vertebrate fish have been found near the base of the Cambrian (01/30/2003), with all their systems appearing fully formed.
    OK, time for the quiz: did this paper mention evolution?  For a change, YES!  But you’ll get a bang out of their one lonely reference: “Cilia are evolutionarily conserved organelles that perform motility, sensory and transport functions and are required for normal vertebrate development and physiology.”  Ha!  You may now laugh your way to the Bank of I.D. and deposit this paper in a C.D. (Certificate of Design), where it will yield high interest, guaranteed.

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