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CHAPTER 30 



found at the completion of development are 

 due to gene-directed changes originating 

 much earlier in development. In fact, we 

 can infer, from the developmental fate of 

 prospective limbs in Creeper embryos, that 

 there are changes produced by a genotype 

 which may precede any morphological 

 changes. We can presume that what the 

 Creeper gene does is to modify the physiology 

 of the individual in such a way that general 

 growth is slowed down, and the prospective 

 fate of certain tissues is fixed, so that the 

 morphological changes later noted are a direct 

 consequence of these changes. The gene- 

 caused physiological changes may be attrib- 

 uted, in turn, to changes in cellular metabo- 

 lism (which deals with the biochemical activi- 

 ties associated with cells). 



We have already seen that genetically deter- 

 mined metabolic changes taking place within 

 certain cells (to produce an abnormal nutri- 

 tional environment) may affect the function- 

 ing of other cells (the differentiation of eye 

 tissue). Let us consider two groups of studies 

 with mice to see if we can learn more about 

 the genetic control of effects produced exter- 

 nal to the cell in which the gene acts. One 

 group of investigations ^ involves a compara- 

 tive study of normal and dwarf mice. These 

 dwarf mice have all of their body parts re- 

 duced in size to the same degree, so they are 

 proportionally dwarfed, due to the presence 

 of an apparently completely recessive gene in 

 homozygous condition. During develop- 

 ment both dwarf and normal mice grow 

 equally fast, at first. Then, the dwarf sud- 

 denly stops growing and never reaches sexual 

 maturity. A microscopic study of the an- 

 terior pituitary gland shows that the gland is 

 very much smaller in the dwarf than it is in 

 the normal mouse. Moreover, certain large 

 cells, normally present, are absent in dwarf 

 pituitaries, and it is these cells which appar- 

 ently secrete growth hormone. That this is 



2 Based upon work of G. D. Snell, of P. E. Smith and 

 E, C. MacDowell, and of T. Francis. 



a case of genetically produced pituitary 

 dwarfism is supported by the following type 

 of experiment. Pairs of dwarf litter mates, 

 about 30 days old, are used. Each day, for 

 30 days, one mouse of a pair is injected with 

 extracts of pituitary glands from dwarf mice 

 (Figure 30-4, B), while the other mouse is in- 

 jected in a comparable way with extracts of 

 pituitary glands from normal mice (Figure 

 30 4, A). During this period of treatment, 

 the former mouse remains essentially dwarf, 

 while the latter grows until it is virtually 

 normal. Here, then, we are dealing with a 

 chemical messenger, pituitary hormone, which 

 regulates growth in general, and whose pres- 

 ence is dependent upon a single pair of genes. 



The second group of studies is concerned 

 with mouse tails. While the normal (+ +) 

 mouse has a long tail, there is one strain in 

 which a shortened tail (Brachyury, or Brachy) 

 occurs.^ Brachy crossed to Brachy produces 

 73 Brachy : K normal offspring, suggesting 

 that a gene Brachy (T) is dominant for short- 

 tailness and recessive for lethality. Brachy 

 mice should be, therefore, T-f. When the 

 embryology was studied of offspring produced 

 following the mating of Brachys with each 

 other (r+ by r+), about 25% of the 

 embryos were normal (+ +), about 50% 

 showed tail degeneration at 1 1 days of devel- 

 opment (r+), and about 25% of the em- 

 bryos (T T) were monsters (Figure 30-5). 

 These monsters had posterior limb buds mis- 

 directed dorsally and zigzag neural tubes; 

 moreover, they had no notochord. Since 

 their whole posterior part was not developed, 

 they could not form a placental connection 

 and died between 10 and 11 days of develop- 

 ment. 



Consider further the T T individual, whose 

 somites in the posterior part of the body are 

 grossly abnormal. It is known, from other 

 embryological work, that proper somite for- 

 mation is dependent upon the presence of 



3 Based upon work of L. C. Dunn, P. Chesley, and 

 D. Bennett. 



