Cell Constitution 



63 



brane, of "typical" tissue cells may be the 

 seat of very dynamic processes involving 

 energy coupling with metabolic processes and 

 possibly alterations in the configurations and 

 interactions of the macromolecular constitu- 

 ents which form the fabric of the membrane. 

 Such processes may be expected to be par- 

 ticularly significant in stages of embryo- 

 logical development and growth. The syn- 

 thesis or activation of enzyme systems 

 (Spiegelman and Steinbach, '45; Boell, '48) 

 and of new proteins and macromolecular 

 constituents exposes the svirface membrane to 

 possible penetration by such svibstances. If 

 the penetration is not readily reversible and 

 ephemeral, these substances will play a role 

 in surface interactions of cells. 



MORPHOGENETIC FIELDS AND THEIR 

 REGULATION 



It is not in the competence of this writer 

 to evaluate, at the biological level, the vari- 

 ous factors involved in the genesis and regu- 

 lation of morphogenetic fields which lead to 

 the orderly development of the embryo. How- 

 ever, it may be useful to suggest a point of 

 view regarding the analysis of such com- 

 plex phenomena and to offer a few sug- 

 gestions as to methods which might prove 

 fruitful. 



First it is necessary to state some of the 

 limiting conditions defining the problem. It 

 seems clear that intimate contact between 

 cells is a necessary condition for induction 

 (see Weiss, '47; McKeehan, '51). To obtain a 

 normal induction for a particular locus the 

 appropriate cells must be in apposition. This 

 is made possible by the orderly movement 

 of cells, bringing acting and reacting cells 

 together at the proper time. What occurs 

 between cells at this time is not known, but 

 induction involves the specific structural 

 and chemical properties of both the acting 

 and reacting cells. The idea that a few hypo- 

 thetical diffusible substances, perhaps occvir- 

 ring in gradients of concentration, may trig- 

 ger off the complex field and regulatory 

 processes seems to have been abandoned as 

 fruitless. Variation in the chemical environ- 

 ment, as by the addition of lithium, ammonia 

 and assorted other inorganic and organic 

 substances, affects the differentiation of in- 

 ductors or the properties of reacting systems 

 but these results seem to be purely empirical; 

 there is no coherent body of chemical facts 

 which explain the effects. 



All this leaves us with respect for the 

 specificity of structure and composition ot 



cells in close contact and for the complexity 

 of the problem, but with no detailed analyt- 

 ical facts from which to proceed. 



Useful in filling this factual vacuum are 

 speculations and working hypotheses based 

 primarily on observed and inferred surface 

 interactions of cells (see particularly Weiss, 

 '50). It seems probable that various types of 

 cell-to-cell and cell-to-substrate interactions, 

 some of which have been discussed in the 

 present chapter, play a significant role in 

 the aggregation of cells into specific tissue 

 or tissue anlagen (see also Loeb, '45; Tyler, 

 '47). However, the complexity of the situa- 

 tion is seen by the necessity of invoking 

 subsidiary hypotheses about the dynamic in- 

 teraction of surface membrane constituents 

 with the cytoplasm and with solutes in the 

 environment. Almost no direct analytical 

 physical or chemical data are at hand con- 

 cerning these surfaces with properties which 

 are, or can be made, specific with respect 

 to developmental processes. 



The failure of the enthvisiastic chemical 

 attack of some years ago is voiced by Holt- 

 freter ('51): ". . . imtil more adequate bio- 

 chemical methods of investigation are found, 

 the burden of elucidating the problems of 

 induction rests more upon the shoulders of 

 the analytically minded morphologist than 

 upon those of the biochemist." But what 

 would constitute more adequate biochemical 

 and biophysical methods? How can one de- 

 vise methods unless the problem to be solved 

 is clearly focussed? It seems clear that an- 

 swers are to be sought chiefly at the molecu- 

 lar level of organization.* At this level the 

 distinctions between morphology and chem- 

 istry largely vanish. But what techniques 

 will provide the "molecidar spectacles" with 

 which to discern the critical phenomena in- 

 volved in embryonic fields and their regu- 

 lation? 



The direct frontal attack on cell ultra- 

 structure has been greatly implemented by 

 modern techniques of electron microscopy. 

 Important new facts may be expected to 

 result from a systematic EM examination of 

 embryological material in thin sections. How- 

 ever, even EM techniques require consider- 

 able development before it will be possible to 



* Many valuable investigations have been made 

 of the relation of biochemical processes, such as high 

 energy phosphate bond transfer (Barth and Barth, 

 '51) and respiratory metabolism (Barth and Sze, 

 '51), to embryonic development. However, these 

 do not lead directly to clues to the mechanism of 

 induction and the regulation of morphogenetic 

 fields. 



