GROWTH OF BLOOD-VESSELS IN FROG LARVAE 39 



That there is a secondary stage in the development of the 

 blood-vascular endothelium, in which the endothelium spreads 

 by sprouting, instead of by the transformation of indifferent 

 cells, has been proven by direct observation. In the transparent 

 fin expansion of the tail of the tad-pole, this process has been 

 watched during life by several observers, especially Golubew 

 ('69), J. Arnold ('71) and Rouget ('73), who have seen blood 

 capillaries send out sprouts, which extended until they met and 

 anastomosed with other sprouts or capillaries and into which a 

 lumen advanced — all without the interposition of outside cells. 

 This view is supported also, among others, by J. Meyer ('53), 

 Bobritzky ('85), His ('69), KoUiker ('86), R. Thoma ('93), 

 Marchand ('01), Ziegler ('05) and Evans ('09 A). While this 

 mode of growth has not been proven by direct observation for 

 all vessels in all animals, and while the existence of other modes 

 of extension is perhaps not necessarily excluded, it is a fair hy- 

 pothesis that this is the universal mode of spreading of the vas- 

 cular endothelium, once it has differentiated, and cannot be 

 abandoned until more convincing objections are brought than 

 have been produced up to the present time. 



It is not the primary purpose of the present study to enter 

 either into the problem as to the time, in embryonic development, 

 at which the second stage begins, nor the problem whether 

 growth by sprouting is the universal mode of spreading during 

 this period. It is rather to consider the problem as to how, in a 

 region where, and at a time in development when growth by 

 sprouting has been repeatedly verified, and after the circulation 

 has become established, the capillaries are transformed into ar- 

 teries and veins; to study the modes of action and reaction of 

 endothelium — the laws which regulate its growth. 



Such a study is by no means new, for it has been, through 

 many years of fruitful investigations, the object of W. Roux 

 and particularly of R. Thoma and numerous coworkers to dis- 

 cover the factors which regulate the growth of vessels, while 

 many others, including Nothnagel ('84), Mall ('03), Evans 

 ('09, A and B, '12) have studied the same problem less 

 extensively. 



