13.
D I F F E R E N T I A T I O N
479
mesenchyme of the same rudiment type so far has been shown to be
effective.
In the case of the salivary rudiment two kinds of mesenchymal
influence have been demonstrated. Under conditions where epithelium
alone spreads as a thin sheet the addition of mesenchyme from nonsalivary sources results in rounding-up of the epithelium and, frequently,
in the formation of a cyst. It seems likely that it was this type of effect
which was observed by Drew (1923) on recombination of cultured
epithelium and non-specific mesenchyme. Only salivary mesenchyme
has the more specific morphogenetic effect on salivary epithelium, i.e.
the promotion of branching and adenomere formation which is antecedent to cellular differentiation. The evidence suggests that the two
effects normally are exerted over quite short range. Epithelial components simultaneously exposed to salivary and non-salivary mesenchyme
on opposite sides of the epithelium respond characteristically to each
mesenchyme, with a sharp line of demarcation at the point of junction
(Grobstein, 1953b). Nonetheless, the effect does not depend upon actual
contact since both mesenchymes exert their characteristic effect across a
thin (20/A) membrane filter (Grobstein, 1953c) which has been shown to
permit only minimal cytoplasmic penetration (Grobstein and Dalton,
1957). Similar trans-filter mesenchymal effects have been demonstrated
for thymus (Auerbach, 1960), skin (Wessels, 1962) and pancreas (Golosow and Grobstein, 1962). In the latter instance the trans-filter system
provides a stroma-free epithelium which forms typical acini, within
which exocrine cytodifferentiation progresses to abundant zymogen
granule formation. This system has been used to investigate the role of
the mesenchymal influence in relation to homotypic effects, leading to
the suggestion that the heterotypic influence may be only indirectly
differentiative—promoting acinar formation or "packaging", which
sets up homotypic relations which are more directly differentiative
(Grobstein, 1962b).
The physico-chemical nature of the mesenchymal influence cannot
yet be specified. The facts outlined suggest that a material is involved
which normally is closely associated with active tissues, either through
limited mobility or limited stability.
McLoughlin (1961a, b) has reported that trypsin-separated epidermal cells of chick-embryo limb-bud orient around a core of PASpositive mucoid material which she believes to be a residuum of material
produced by the normally underlying mesenchyme. In recombination
of epidermis with limb mesenchyme she finds similar orientation of the
epidermal cells, and interprets this as reaction not to the fibroblasts of
the dermis but to the intercellular material they produce. Epidermis
combined with mesenchyme from gizzard fails to keratinize and under-
D I F F E R E N T I A T I O N
479
mesenchyme of the same rudiment type so far has been shown to be
effective.
In the case of the salivary rudiment two kinds of mesenchymal
influence have been demonstrated. Under conditions where epithelium
alone spreads as a thin sheet the addition of mesenchyme from nonsalivary sources results in rounding-up of the epithelium and, frequently,
in the formation of a cyst. It seems likely that it was this type of effect
which was observed by Drew (1923) on recombination of cultured
epithelium and non-specific mesenchyme. Only salivary mesenchyme
has the more specific morphogenetic effect on salivary epithelium, i.e.
the promotion of branching and adenomere formation which is antecedent to cellular differentiation. The evidence suggests that the two
effects normally are exerted over quite short range. Epithelial components simultaneously exposed to salivary and non-salivary mesenchyme
on opposite sides of the epithelium respond characteristically to each
mesenchyme, with a sharp line of demarcation at the point of junction
(Grobstein, 1953b). Nonetheless, the effect does not depend upon actual
contact since both mesenchymes exert their characteristic effect across a
thin (20/A) membrane filter (Grobstein, 1953c) which has been shown to
permit only minimal cytoplasmic penetration (Grobstein and Dalton,
1957). Similar trans-filter mesenchymal effects have been demonstrated
for thymus (Auerbach, 1960), skin (Wessels, 1962) and pancreas (Golosow and Grobstein, 1962). In the latter instance the trans-filter system
provides a stroma-free epithelium which forms typical acini, within
which exocrine cytodifferentiation progresses to abundant zymogen
granule formation. This system has been used to investigate the role of
the mesenchymal influence in relation to homotypic effects, leading to
the suggestion that the heterotypic influence may be only indirectly
differentiative—promoting acinar formation or "packaging", which
sets up homotypic relations which are more directly differentiative
(Grobstein, 1962b).
The physico-chemical nature of the mesenchymal influence cannot
yet be specified. The facts outlined suggest that a material is involved
which normally is closely associated with active tissues, either through
limited mobility or limited stability.
McLoughlin (1961a, b) has reported that trypsin-separated epidermal cells of chick-embryo limb-bud orient around a core of PASpositive mucoid material which she believes to be a residuum of material
produced by the normally underlying mesenchyme. In recombination
of epidermis with limb mesenchyme she finds similar orientation of the
epidermal cells, and interprets this as reaction not to the fibroblasts of
the dermis but to the intercellular material they produce. Epidermis
combined with mesenchyme from gizzard fails to keratinize and under-