306
EDGAR
ZWILLING
elaboration of distal limb structures under the influence of the ectoderm
(ridge, cap) which, as a consequence, is responsible for distal outgrowth
of the limb. If this system is deprived of the ectodermal ridge before all
of the presumptive limb elements are elaborated there is a halt in the
formation of additional limb elements, but those which have been laid
down may continue to develop their typical form and will grow (intercalary growth) at nearly the usual rate. The result is a limb which is
deficient in distal elements but whose proximal parts are quite normal.
Exactly which distal parts will be missing depends on when the ridge is
removed.
(4) The persistence of the ectodermal thickening as an active influence
on continued elaboration of distal limb elements depends upon some
factor (apical ectoderm maintenance factor) which is present in limbbud mesoderm. While little is known about the nature of this factor,
evidence allows us to postulate the following:
(a) In the absence of the maintenance factor the ectodermal thickening regresses; either by degeneration or by alteration (flattening)
of its form.
(b) The maintenance factor is distributed asymmetrically in the
limb-bud mesoderm; normal asymmetries in the developing limb,
different for different limbs and typical of each type, are a
consequence since sequential outgrowth occurs in association with
the active, thickened ridge.
(c) Anomalous limb patterns (Polydactyly, amelia, ectromelia, etc.)
result from atypical distribution of the maintenance factor. A
second concentration of the factor (or a more extensive distribution pre- or post-axially) may result in a more extensive ectodermal
ridge and, as a consequence, supernumerary limb parts. The
absence of the factor (or its diminution) leads to regression of the
ridge and consequent absence of parts of a limb. (N.B. similar
limb deficiencies may result from later degeneration of fully or
partially elaborated limb parts.)
(d) The maintenance factor is transmissable in a proximo-distal
direction. Under experimental conditions a region of low concentration may be augmented by an underlying area of higher
concentration.
(e) The asymmetries of the ectodermal ridge (i.e. variation in its
thickness and active influence on sequential outgrowth) conform
to the pattern of maintenance factor distribution in the limb
mesoderm.
(5) Limb type properties (i.e. fore-limb vs. hind-limb) are resident
in the mesoderm.
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