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J. MILAIRE
simultaneous elaboration of both zeugopodial presumptive areas. It is
known that although the a.e.r. differentiates in only the postaxial part
of the limb bud, the whole marginal ectoderm (pre- as well as postaxial) shows specific histochemical properties during the asymmetrical
growth of the limb bud. A third and important wave of inductive activity occurs when the a.e.r. becomes completely differentiated both
morphologically and histochemically. This new ectodermal influence
promoting the growth of the footplate and the differentiation of most
autopodial precartilages is so strong that it alters the usual proximodistal spreading of chondrification. The only reasonable interpretation
of the fact that the carpal and metacarpal precartilages chondrify
sooner than the more proximal elements (radiale, ulnare, intermedium
and centrals) is that a sudden acceleration of this process takes place in
the former. The proximal elements have most probably been induced
before the limb paddle started growing, i.e. before the a.e.r. entered the
phase of maximal activity. But although they were the first to be induced, they have been preceded in chondrification by the more distal
elements which were subject to a specially strong ectodermal influence.
The normal proximo-distal sequence of chondrification is then reestablished in the formation of phalanges, which are successively differentiated by the decreasing and more restricted inductive activity of
the degenerating a.e.r.
The order of origin of limb cartilages in the mammalian limb development is thus in full agreement with that demonstrated in chick and
Xenopus embryos by experimental methods.
In his recent review of limb morphogenesis, Zwilling (1961, p. 321)
seems to think that in our work on the rat embryo (Milaire, 1956), we
found that the proximal parts of mammalian limb buds are successively
added behind the distal structures. We would like to correct this misunderstanding, for we clearly demonstrated the classical proximodistal sequence of origin of limb parts in the rat embryo (Milaire, 1956,
p. 375).
IV. Conclusions
In all vertebrates, a large area of the dorsal somatopleure is potentially able to develop into limb tissue before entering its proliferating
stage. The usual histochemical changes of proliferating cells may be
demonstrated in the whole of this structure when it starts growing and
forms Wolff's crest. However, none of the experimental or descriptive
data enable us to understand why this mesodermal proliferation rapidly
breaks off in the intermediate portion of Wolff's crest and continues at
its extremities, where it leads to the initiation of limb development.
There is no evidence that competitive phenomena occur between the
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