THE BLOOD CELLS 77 



certain centers are dcNeloped from uicscnchyme in (liH'erent regions 

 of the body. A study of the vertebrates, l:)eginning at the lowest 

 end of the scale with the fish and progressing through to the mam- 

 mals, presents a series in which evolution of l)l()()d-forming centers 

 may be traced and compared with similar stages in the embryonic 

 development of mauniuils. 



The earliest hema])oietic center to ap])ear is found in the case of 

 the hagfish, where a diffuse arrangement of proliferating and differ- 

 entiating blood cells occurs in the connective tissue of the gastro- 

 intestinal tract. In other forms, blood-forming tissue becomes more 

 localised and concentrated in certain regions of the tract, as in the 

 spiral valve of the lami)rey. A still further condensation gives a 

 spleen that is bound into the wall of the stomach or intestine. Such 

 centers are supported by a network of connectixe tissue in which the 

 blood cells are proliferating in close contact with sinusoidal cajiillar- 

 ies leading into the venous system. In ganoids the spleen is an 

 extra-enteral organ attached to the mesentery; the submucosa of 

 the intestinal tract may still retain the capacity to develo}) granu- 

 locytes, but red cell formation centers in the spleen. In the higher 

 fishes and in the amphibia, the spleen becomes the main center for 

 blood cell formation. Mesenchyme cells in other localities, such 

 as the cai)sule of the gonads and in the liver, also play a role in 

 blood cell formation. With the development of hollow bones in 

 reptiles, birds, and mammals, the center for production of the red 

 cells and granulocytes shifts to the bone-marrow, the spleen playing 

 its major role only in early devel()i)ment. With this shift to the 

 bone-marrow the production of agranulocytes, ])rimarily lym])h()- 

 cytes, is taken care of by lym])hoid tissue in the form of lymph 

 nodes and the spleen. 



Except in embryonic life, where blood cells form in the developing 

 vessels, blood cell formation usually takes place extravascularly. 

 In the hemapoietic centers there is a network of reticular cells and 

 fibers supporting the proliferating primitive blood and lymph cells 

 derived from mesenchyme. Following a period of differentiation 

 into the ^•arious types of cells the fully differentiated red or white 

 cells enter the venous sinuses which form a network through such 

 centers. In mammals, where lymphocyte production does not com- 

 monly occur together with that of the other myeloid elements, which 

 are primarily produced in the marrow, the lymphocytes enter lymph 

 vessels supplying the lymphoid tissue, or, as in the spleen, enter 



