The origin of the term “chimera” stems from ancient Greek mythology.  The Chimera (or Chimaera) was a creature that is part lion, part goat, and part snake (see image below) that terrorized the city of Lycia.  As an attempt to send the hero Bellerophon to his demise, he was challenged to kill the Chimera.  Bellerophon surprisingly was successful at ridding Lycia of their burden with the aid of Pegasus and his spear.  More on the mythology (from greekmythology.com).
           

16th century print of Bellerophon slaying the Chimera

The Chimera of Arezzo Statue

     















    Because of the creature’s unique composition, the term “chimera” is used to describe, in our case, animals that have been constructed to include genetic lineages from two different strains of animals.  For example, by taking an 8-cell stage embryo from a black rat and another from a white rat, when you combine them to produce an aggregate embryo and place it in a surrogate mother, the offspring will present features of the two different colored rats.  Namely, the offspring will have black and white stripes.  These multizygotic mosaic animal offspring are called chimeric animals.

 

Formation of Aggregate Embryo

Formation and expansion of eGFP (jellyfish green flourescent protein) TG <--> +/+ chimeric blastocyst

Expression of eGFP in fur patches [The eGFP transgenic rats used to produce chimeras were the kind gift of Carlos Lois]

   


     

These zebra-like patches of fur on the chimeric rats are the most obvious sign of feature blending, but not the only place where these patches are present.  With appropriate markers, patches are also visible in the animal’s organ tissue, like the adrenal gland, liver, and corneas.

 

Rendering of a Part of Rat Adrenal Cortex Tissue

Rendering of a Part of Rat Liver Tissue

Rendering of a Part of Rat Cornea Tissue

 

    
  

    The cellular patches do not just form randomly; rather they develop in particular patterns.  These patterns are conserved and regulated, that is, they vary between the tissue types in the animal, and the patterns are the same from animal to animal.  These patterns appear to form in an algorithmic manner called a fractal.  Although very complicated, fractals can be formed rather simply.  The animation below shows the formation of a specific type of fractal called the Koch snowflake.

 

 

    Even though the numerous varieties of fractals all appear vastly different, they all exhibit a common characteristic; they all have fractal dimensions greater than one (D > 1).  There are a couple of ways to measure the fractal dimension, but they typically all come to the same result.  One way is the yardstick method.  In the case of the cellular patches, the perimeter of the patch, L(e), was measured using a yardstick of length e.  The yardstick’s length was changed and the perimeter is measured again.  The varying lengths of the yardstick were spaced logarithmically.  The fractal dimension, D, is then calculated as follows:

            D = 1 – log (L(e)) / (log (e))

Analysis of tissue samples shows that the patches have fractal dimensions greater than one, and therefore are fractals.

    Because fractals are formed using specific recursive rules, and because the patches have been shown to be fractal, two things become apparent.  First, the development of the patches and therefore the tissue itself may be governed by similarly simple and specific rules, and secondly, that the development of the patches as well as the tissue can be modeled mathematically.

 

Conclusions:

    The patterns exhibited in tissues of rat chimeras could be explained by recursive and iterated cell division schemes.  These cell division schemes can then be represented with computer models (See Lab Publications below).

    Based on this information our goals are to firmly establish:  a 3-D volumetric representation of the patch geometry in the chimera’s tissue, a robust computer models which are predictive of patch tissue growth, and a volume based analysis of the fractal dimension of the patch tissue.

Lab Publications (Comprehensive List):
Iannaccone, P., Morley, S., Skimina, T., Mullins, J., Landini, G.,  Cord-like mosaic patches in the adrenal cortex are fractal: implications for growth and development.  FASEB J.,  17(1):41-3, 2003.  Epub 2002 Nov 15. [abstract]

Landini, G., Iannaccone, P.,  Modeling of mosaic patterns in chimeric liver and adrenal cortex: algorithmic organogenesis?  FASEB J., 14(5):823-7, 2000. [abstract]

Iannaccone, P.,  Morley, S., Skimina, T.,  and  Landini,.G.,  "Fractal Geometry of Adrenal Cortex Mosaic Patches: Implications for Growth and Development." In: Fractals and Beyond: Complexities in the Sciences. Ed. Miroslav M. Novak., World Scientific, Singapore,  pp. 53-63, 1998.

Iannaccone, P., and Khokha, M., Eds.  Fractal Geometry in Biological Systems: An Analytical Approach.  Boca Raton: CRC Press, 1996.


References:
Eric W. Weisstein.  "Fractal." From MathWorld--A Wolfram Web Resource.
http://mathworld.wolfram.com/Fractal.html