222 PHYSIOLOGIC GENETICS 



GENES IN EMBRYONIC DEVELOPMENT AND DIFFERENTIATION 



Many skeletal abnormalities and derangements of organs have been shown to 

 result from genie action during embryonic development. Retrograde analysis, 

 studying the mutant phenotype at progressively earlier stages, is clearly an effective 

 tool for locating place and time of initial genie action but does not always help in 

 determining its nature. 



Frequently there is evidence of inductive failure. An abnormality frequently 

 associated with the Short-Danforth gene (Sd) is reduction or absence of the kidney, 

 which has been demonstrated to result from reduced length of the ureteric outgrowth. 

 In some cases there is no contact with competent tissue, and no induction of meta- 

 nephros. 440 In addition to the previously mentioned genes causing choreic move- 

 ments through tissue dedifferentiation, a series of genes with very similar behavioral 

 effects act in a very different pattern by preventing normal induction of the middle ear, 

 each gene acting in a different and specific way. 499, 818 



The most extensively studied series of genes acting through induction is the 

 Brachyury or T series. In addition to the normal wild-type allele, one dominant (T) 

 and numerous recessive (t x ) alleles are known; additional instances of mutants have 

 frequently been found in populations of wild mice. Most of the homozygous types 

 are lethal before birth, the time of death varying greatly among alleles, but a few are 

 viable. Only T leads to tail reduction in combination with the wild-type allele, and 

 all Tt x combinations lead to short or absent tails. The homozygous lethal alleles of 

 the T'-series fall into five classes according to time and nature of original genie action. 76 

 Primary action of T seems to be inductive failure at approximately the ninth or tenth 

 day of development resulting from degeneration of the chorda-mesoderm. 204 - 502 The 

 / 12 / 12 homozygote shows the earliest lethal effect, failure of blastocyst formation as- 

 sociated with defective trophectoderm. 1221 In t°t° homozygotes the inner cell mass 

 fails to differentiate into embryonic and extra-embryonic ectoderm. 439 In a group of 

 five relatively early-acting t w alleles (collected from the wild), the first microscopically 

 visible defect is pyknosis in the basal plate of the neural tube around the seventh day 

 of embryonic life. Homozygotes of four relatively late-acting t w alleles show their 

 first abnormality on the ninth or tenth day of development, as pyknosis in the ventral 

 portion of the hindbrain, the notochord and mesoderm being normal. 76 These 

 interesting findings have many embryologic implications for which the reader is 

 referred to the original papers. Several points are, however, worth mentioning in 

 connection with general principles of genie action. Bennett and Dunn 77 point out that 

 although the first microscopically visible defect in all t homozygotes is in ectoderm, it is 

 still impossible to decide between local genie action deranging metabolism of the 

 embryonic ectoderm and genie action in the endoderm leading to improper nutrition 

 and consequent death of ectodermal cells. In each case, however, the ectodermal 

 degeneration is associated with failure of induction of mesodermal tissues. The neural 

 tube of both TT and t w t w embryos is capable of inducing cartilage in vitro™ In 



