464
C L I F F O R D G R O B S T E I N
results. It seems more useful to state briefly the general lessons of the
past, and to concentrate on the issues which now face us. The latter are
emerging in the considerably more incisive literature of the past few
years, and it is to this literature that I will largely refer. With a few
exceptions I shall limit myself to culture of mammalian and avian
tissues. I shall discuss briefly the criteria by which differentiation may
be recognized and measured in culture, outline what seem to be the
chief current problems, and then touch on what is known of the
influence on cytodifferentiation of the general culture environment, of
other cells of like type (homotypic), and of other cells of unlike type
(heterotypic). The whole will be summarized by an effort to relate
knowledge of differentiative behavior in vitro to the general question of
differentiative mechanisms.
I I . C R I T E R I A OF D I F F E R E N T I A T I O N
The term differentiation is applied here to the progressive increase of
diversity within an organism during its life history. Cytodifferentiation, on
which major emphasis will fall, designates the changes in cells which
occur during developmental diversification of the parent organism.
Differentiative cellular changes are part of a broad spectrum of modifiability of cell properties, some of which are labelled functional, others
adaptive, still others mutational, etc. At current levels of understanding
it is important not to erect too sharp boundaries between the various
categories of cell change, but it is also important not to confuse
categories which may prove to have very different underlying
mechanisms. Given the wide variety of changes now known to occur in
cultured cells (Swim, 1959; Grobstein, 1959a; Moser, 1960; Salzman,
1961) it is essential to have a standard of reference for those which are
to be regarded as differentiative. Such a reference is provided by the
normally developing embryo, within which the problem of differentiation was first defined. In these terms, differentiation refers not to any
alteration and diversification of properties which may appear or exist
in cultured cells and tissues, but only to those which probably repeat
processes occurring in development in vivo. This does not exclude other
changes from relevance; it merely centers attention on differentiative
phenomena in the embryo as the focal problem.
In general, differentiative criteria may be said (Grobstein, 1959a) to
fall into four categories: morphological, behavioural, chemical, and
developmental. Morphological characterization of differentiation
includes the traditional techniques of histology and cytology, the more
modern approach via such improvements as the phase microscope, and
C L I F F O R D G R O B S T E I N
results. It seems more useful to state briefly the general lessons of the
past, and to concentrate on the issues which now face us. The latter are
emerging in the considerably more incisive literature of the past few
years, and it is to this literature that I will largely refer. With a few
exceptions I shall limit myself to culture of mammalian and avian
tissues. I shall discuss briefly the criteria by which differentiation may
be recognized and measured in culture, outline what seem to be the
chief current problems, and then touch on what is known of the
influence on cytodifferentiation of the general culture environment, of
other cells of like type (homotypic), and of other cells of unlike type
(heterotypic). The whole will be summarized by an effort to relate
knowledge of differentiative behavior in vitro to the general question of
differentiative mechanisms.
I I . C R I T E R I A OF D I F F E R E N T I A T I O N
The term differentiation is applied here to the progressive increase of
diversity within an organism during its life history. Cytodifferentiation, on
which major emphasis will fall, designates the changes in cells which
occur during developmental diversification of the parent organism.
Differentiative cellular changes are part of a broad spectrum of modifiability of cell properties, some of which are labelled functional, others
adaptive, still others mutational, etc. At current levels of understanding
it is important not to erect too sharp boundaries between the various
categories of cell change, but it is also important not to confuse
categories which may prove to have very different underlying
mechanisms. Given the wide variety of changes now known to occur in
cultured cells (Swim, 1959; Grobstein, 1959a; Moser, 1960; Salzman,
1961) it is essential to have a standard of reference for those which are
to be regarded as differentiative. Such a reference is provided by the
normally developing embryo, within which the problem of differentiation was first defined. In these terms, differentiation refers not to any
alteration and diversification of properties which may appear or exist
in cultured cells and tissues, but only to those which probably repeat
processes occurring in development in vivo. This does not exclude other
changes from relevance; it merely centers attention on differentiative
phenomena in the embryo as the focal problem.
In general, differentiative criteria may be said (Grobstein, 1959a) to
fall into four categories: morphological, behavioural, chemical, and
developmental. Morphological characterization of differentiation
includes the traditional techniques of histology and cytology, the more
modern approach via such improvements as the phase microscope, and