342 PRINCIPLES OF EMBRYOLOGY 



be expected, this affects all these structures for which the hormone is 

 important, so that the animal develops as a dwarf. 



Griineberg (1948) has shown that many other cases in which a gene 

 has manifold and widespread effects can be explained in a similar way. 

 One of the best-known examples is that of a certain lethal in rats. Animals 

 homozygous for the gene show a very diversified complex of symptoms, 

 which eventually lead to their death at an early age. Griineberg (1938) 

 argues that all (or nearly all) the symptoms can be plausibly considered 

 to be secondary consequences of an original hypertrophy of the cartilage. 

 The network of causation which he postulates in this case is shown in 

 Fig. 15.6. Falconer, Fraser and King (195 1) have described another case, 

 in which a gene 'crinkled' in mice produces a large number of different 

 effects which they suggest can be almost entirely accounted for as the 

 results of a suppression of hair follicle formation between twelve and a 

 half and seventeen days of gestation and after birth. The suggestion that 

 all the effects in this case are actually secondary consequences of one 

 initial abnormality receives very strong support from the fact that 

 another different gene tabby also produces (in single dose) exactly the same 

 syndrome. If each symptom was brought about by a separate reaction of 

 the gene, such a parallelism could not be expected unless the crinkled and 

 tabby genes were identical, which the genetical evidence shows them not 

 to be; whereas if there is one single underlying cause for the syndrome, it 

 is easy to imagine that two or more different genes may affect the basic 

 process and thus produce the same complex end-result. 



Hadom (1948^7, 1950, 1951^) has paid particular attention to the 'pattern 

 of manifestation' of a gene, i.e. the particular collection of organs whose 

 development it alters. He studied certain 'lethals' in Drosophila, that is 

 genes whose effects are so profound that individuals homozygous for 

 them do not survive. He emphasises, first, that there are critical periods 

 of development at which death tends to occur. Thus many lethals are 

 known which produce death at the end of the embryonic period, and 

 again there are many for which the time of death is at puparium forma- 

 tion, or at emergence; but there are very few which kill during the 

 middle of larval life. These sensitive periods are the times when a great 

 deal is going on in the epigenetic system, so that slight abnormalities in 

 the tissues, which may have been produced considerably earlier, will then 

 cause drastic effects. They have also been referred to as 'epigenetic crises', 

 and are of various grades of severity. 



Hadom went on to show that if the phenotypes produced by the 

 lethal genes are closely examined, each gene wiU be found to cause a 

 characteristic pattern of damage, exhibited either by the death and 



