ORGAN DEVELOPMENT IN VERTEBRATES 27I 



covered by epidermis which does not differ from that of the rest of the 

 body. The mesoderm cells at first show little sign of particular differen- 

 tiation, but form a rather loosely aggregated mass of mesenchyme. As 

 the limb elongates, the cells towards the centre of it become more tightly 

 packed, forming a number of condensations within the mesenchyme 

 (Fig. 20.5, p. 429V These group themselves into the pattern of the skeletal 

 elements of the normal limb, and gradually differentiate, first into cartil- 

 age and then into bone. Meanwhile the remaining mesenchyme develops 

 into the muscles. 



The development of the limbs has been very extensively studied, and 

 provides examples of a number of points which cannot be so well illus- 

 trated in any other field. 



At about the time of the First World War, Ross Harrison (191 8) began a 

 long study on the polarity and asymmetry of the limbs of urodeles. The 

 subject was also pursued by a number of his students, such as Detwiler 

 and Swett. The most recent summary of the extensive literature of this 

 group of workers is that of Swett (1937) and the main contribution since 

 then is an extensive and important work by Takaya (i94i)- 



It is clear that a fully developed limb must be either a right or a left 

 limb and that these two have essentially different asymmetry, being, in 

 fact, mirror images of one another. The genesis of tliis asymmetry can 

 be studied by excising the presumptive limb region from an embryo and 

 grafting it back in such a way as to change the relation between the 

 polarity of the graft and that of the host body. Consider, for instance, the 

 forehmb of a newt. In the tail-bud stage the region from which this limb 

 will develop is represented by a circular area on the side of the body just 

 below somites 3 and 4. Suppose that the limb area on the left side of a 

 newt embryo was cut out, then pushed up to the dorsal midline and down 

 the other side, and eventually grafted in place of the right limb area, 

 which had been previously removed. Then it is clear that its anterior end 

 would still point towards the anterior end of the whole body, and its 

 exterior side would still lie towards the exterior, but its dorsal side would 

 now be below and its original ventral side uppermost. Such an orientation 

 is described by saying that we have reversed the dorso-ventral axis of 

 the graft but left its antero-posterior and medio-lateral axes unchanged. 

 We could, of course, reverse both the antero-posterior and dorso-ventral 

 axes leaving the medio-lateral one unchanged, by making a circular cut 

 around the limb-forming area on one side and then rotating the area 

 through 180 degrees about an axis perpendicular to its surface before 

 allowing it to heal in again. By a variety of such methods one can, in fact, 

 reverse at will any particular axis or combination of axes. After such 



