158 



The Nucleus and Cytoplasm in Development 



effects of the mutant genes were accom- 

 panied by internal effects. Since the sperma- 

 thecae had been selected arbitrarily as pos- 

 sible indicators of multiple genie effects, it 

 may be concluded that many other traits 

 would likewise exhibit specific phenotypes as 

 the result of different mutant alleles. 



The phenomenon of multiple effects of a 

 gene poses the important problem of mul- 

 tiple primary gene action versus unitary 

 primary gene action with secondary, mul- 

 tiple developmental results. In several in- 

 stances, it has been possible to trace back 

 developmentally the multiple observed ef- 

 fects to a single primary cause. Thus, in the 

 Frizzle fowl, the abnormality of the feathers, 

 which wears off quickly, is the initial event 

 which seems to account for all others. The 

 loss of plumage results in loss of body heat, 

 this in turn in subnormal body temperature 

 and increased metabolic rate. "From here, 

 one chain of adaptations leads to accelera- 

 tion of heart rate, ventricular hypertrophy, 

 enlarged blood volume, and excessive size 

 of spleen. In order to sustain the accelera- 

 tion of these vital processes more food is 

 consumed and this, in turn, produces en- 

 largement of the intestinal parts, hypertro- 

 phy of the pancreas and of the kidneys. A 

 heavy burden falls on the adrenals and thy- 

 roid. . . . Reduced vaporization is another 

 adjustment useful to the body economy." 

 (Landauer, '46.) 



In the "myelencephalic blebs" (mice) the 

 primary event is the appearance, diu-ing em- 

 bryonic stages, of large blisters under the 

 skin of the head (Bonnevie, '34). These 

 blisters are filled with fluid of cerebrospinal 

 origin which has escaped through a foramen 

 in the myelencephalon. At first, these blebs 

 move under the skin to different parts of 

 the body. Finally, they come to rest and 

 gradually disappear before the termination 

 of gestation. Since the blisters are under in- 

 ternal pressure, it is not surprising that dis- 

 turbances of development result in their 

 neighborhood. Those blebs which come to 

 rest in the region of the developing eye may 

 produce eye defects, while others whose final 

 position is at the limb buds cause the various 

 types of foot abnormalities. 



Other developmental "pedigrees of causes" 

 of multiple genie effect have been worked 

 out, in both rats and mice, by Grvineberg 

 ('38). He is inclined to postulate that all 

 pleiotropic genie action depends on a single 

 primary effect. It can, indeed, not be doubted 

 that developmental studies of multiple gene 

 effects not only repeatedly have succeeded 



in tracing back the pedigree of causes to a 

 single basic event but also that more such 

 results can be expected in cases which still 

 defy such an analysis. However, there seems 

 to iDe no a priori reason why primary gene 

 action may not sometimes be of multiple 

 nature. Genie action has often been com- 

 pared to that of enzymes, and intrinsic iden- 

 tity of genie action and gene-controlled en- 

 zymatic action has been suggested (Beadle, 

 '45; Emerson, '45). It is significant, from 

 this point of view, that at least one enzyme, 

 tyrosinase, seems to have two very different 

 activities (Nelson and Dawson, '44). There- 

 fore, the existence of multiple primary ac- 

 tion of a gene would be compatible with 

 concepts which consider genie action within 

 the frame of protein chemistry. Actvially, it 

 will be very difficult to decide between 

 multiple primary action and early diversifi- 

 cation of unitary action unless the details 

 of the earliest gene-controlled cellular phys- 

 iological processes are fully vmderstood. An 

 example, from Neurospora, may illustrate 

 this statement. A certain mutant of this 

 fungus is unable to synthesize adenine; in- 

 stead, it makes a purple pigment not pres- 

 ent normally (Mitchell and Houlahan, '46). 

 Although a mutant allele which can syn- 

 thesize redviced amounts of adenine and at 

 the same time forms the purple pigment has 

 not yet been described, we may assume its 

 existence for purposes of this discussion. 

 There woidd, then, exist an allele with two 

 intracellular effects, adenine synthesis and 

 pigment formation. However, these two ef- 

 ects would still be found to depend on a 

 single activity, since it is probable that the 

 pigment is nothing but a derivative of a 

 precursor of adenine. In a cell with a normal 

 allele the precursor is transformed into aden- 

 ine, but in the mutant cell with its impeded 

 transformation to adenine, the precursor 

 accumulates and becomes observable as a 

 "second" gene effect. 



In a mvdticellular organism the problem 

 of multiple versus unitary gene action refers 

 not only to the primary action at the molecu- 

 lar level but also to the site of action in the 

 organism as a whole. The abnormality of 

 feathers in the Frizzle fowl, which is the 

 primary event in the development of the 

 various symptoms, has a single site, although 

 extensive in space, namely, all cells of the 

 epidermis concerned in the production of 

 feathers. Similarly, in mice with myelen- 

 cephalic blebs, there is a primary site of 

 developmental abnormality, the region of the 

 embryonic brain. On the other hand, in 



