DIFFERENTIATION AND PROTEIN SYNTHESIS 91 



be found occasional bunches of cilia, finger-like protrusions or mucin- 

 containing pockets. 



The basal membrane once established appears to provide a suitable 

 substratum for the crystallization of fibrils of collagen, the soluble precursor 

 of which (tropocollagen) is thought to be produced by the mesodermal 

 fibroblasts (Fig. 38 and Plate 9). 



Essentially similar observations concerning the development of inter- 

 cellular adhesion between the epidermal cells of chicken embryos have 

 also been made by the present writer. 



Thus the key steps in epidermal differentiation appear to be : 



(a) The appearance of close contacts between cells which results in the 

 monolayer of surface cells acquiring a coherent epithelial character. 

 Differentiated features (intracellular filaments, cilia and mucin droplets) 

 appear on the outer surface about the same time and recall the normal 

 differentia found in cells with free surfaces (p. 44). 



(b) The appearance of a basal membrane — a diffuse sheet underlying 

 the basal layer cells. 



(c) At this stage the basal membrane cells are (to judge from their 

 fine cytology) still polyfunctional. They have the dispersed basophilic 

 reticulum of a secreting cell (collagen ?). Collagen in any event rapidly 

 accumulates beneath them; the mesodermal fibroblasts also spread out 

 over the sheet and appear to secrete directly against the collagen mesh- 

 work. By this stage the definitive histology is established. The explanation 

 of these events must be speculative at the present time but, with this 

 caution in mind, it is worth while proposing what are in effect working- 

 hypotheses as follows (Fig. 38): 



(i) The first differentiations of superficial cells (cilia, mucin formation, 

 synthesis of intracellular fibrils) are similar to those noted in single cells 

 and they appear because the surfaces are free. While this explains nothing, 

 it refers the problem to a larger one not confined to the Metazoa. In these 

 early stages most of the cell surfaces are free and, to judge from their 

 convolutions, in active movement. They are little removed from free- 

 living cells, as is shown, indeed, by Holfreter's observations on cells, 

 liberated from amphibian embryos by reagents dissolving the weak inter- 

 cellular adhesive, which were able to assume an amoeboid habit and move 

 about. 



(ii) Organized multicellular differentiation is initiated by intercellular 

 adhesion which commences between the contiguous portions of cell 

 membranes facing the external environment and from there travels 

 inwards. It is assumed that this is because the cells at this point start to 

 secrete an intercellular cement; their surfaces become sticky. This would 

 be the decisive metazoan feature. 



