The like and the unlike
A CURIOUS dichotomy in the development of higher animals (plants are exceptional in this respect) has come to light following recent research. During the course of embryogenesis, a fertilised egg goes through a series of multiplications that, along with growth, are responsible for a tremendous increase in the number of cells as well as in overall size. Accompanying this complicated process is that of differentiation, where- by various groups of cells take on differ- ent specialised functions; for example, some become muscles, others turn into skin or liver and so on.
These drastic differences in functions reflect in the actions of some genes in certain cells. Each differentiated cell contains specialised proteins that constitute a signature of a particular cell type (for example, haemoglobin is characteristic of blood). Now, the presence of a protein signals the activity of the gene responsible for encoding that protein. Therefore, these qualitative differences in protein content, which are parallel to differences 'n function, reflect the fact that some genes are active in some cells and other genes in other cells. The dichotomy lies in the fact that this difference occurs in spite of all cells being identical in terms of their genetic makeup. Scientists have racked their grey matter over whether it might not be possible to take advantage of the genetic identity of all the cells in a body for the purpose of replacing tissue or organs that are damaged or lost. The more ambitious have gone steps ahead: they have asked whether an entire organism could not be cloned -recreated, as it were -starting from a single differentiated cell.
To be sure, this does happen in the simpler fonns of life. Primitive animals like the hydra can reproduce by bud- ding, which is equivalent to the concept of cloning itself. Vertebrates can partially replace missing parts of the body even if not replace themselves entirely. Tadpoles and lizards show that it is possible to regenerate tails and limbs. However, it has so far proven difficult to duplicate the feat performed by the hydra and regenerate an entire higher animal by starting with a few cells. B Rinkevich, Z Shlemberg and L Fisehlson of the department of zoology in Tel Aviv University, Israel, have recently reported the successful cloning in the laboratory of an animal that straddles the drive-in line between invertebrates and vertebrates. It has, therefore, acquired the name of urochor- date or the primitive chordate; the chorda is the precursor of the backbone (Proceedings of the us National Academy of Sciences, Vol92).
The creature is known as the ascidian or tunicate. In its larval stage, it looks like a tad- pole and can swim by flexing a rod-like organ called the notochord, the forerunner of the backbone. But after metamorphosis, the adult that develops is to all outward appearances a sessile (an animal that lives permanently attached to a sub- strate) invertebrate.
Rinkevich's group worked with the colonial species Botrylloides, also known as the sea squirt. A fertilised egg of Botrylloides normally gives rise to over 100 different cell types organised in a structure called the zooid. What Rinkevich's group did was to break up mechanically a colony of Botrylloide into its constituent zooids. After a zooid was excised, it tended to develop one or more vascular buds. The starting point was a mixture of blood cells enclosed within a blood vessel.
The initial steps in the process of budding were "anarchic" or "chaotic", but this gradually gave way to an ordered state. The first sign of order was a to-and-fro rhythmic flow of blood within an isolated vessel or fragment. In the course of a few hours to a few days, the vessels ramified and set up a com- plex interconnected structure. Vascular buds were generated within this arrangement.
Further cell divisions led to the formation of a hollow, ball-like structure, which resembled something called the blastula -an universal feature of the development of an animals. The blastula forms some 10 or so cell divisions after an egg is fertilised. After the blastula -like stage, the further steps of regeneration appeared to consist of a recapitulation of normal development and culminated in the appearance of a typical zooid.
This is the second account of the complete regeneration of a colonial urochordate; these was a similar report some 40 years ago by two Japanese scientists, H Oaka and H Wanabe. Its significance cannot be overstressed. It opens up, if only tentatively at present, the possibility of understanding how genetic pathways that have led to a seemingly terminal state of differentiation- in this case, into blood -can be reversed. There is a close resemblance between these observations made on the ascidian and something called a teratocarcinoma, which is caused by the aberrant differentiation of early embryonic cells. A teratocarcinoma leads to the formation of a tumor that is made up of a wide variety of tissues including bone, teeth and muscle. Teratocarcinomas have been studied in humans and mice as possible models for how normal development works. Similarly, the unique regeneration of botryllid ascidians may serve as a novel model for development.
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