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CHARLES
Ε.
WILDE
they derive certain metabolites remains to be discussed. A microenvironment cogent to the processes of cellular differentiation must
subsume the totality of molecular species in the non-living immediate
environment and also those readily exchangeable between cells in the
vicinity or between cell and non-protoplasmic space. Thus cues may be
passed into the micro-environment from adjacent cells and thence to
the differentiating cell with or without intervening reactions in the
immediate non-protoplasmic milieu. The micro-environment is the most
convenient area for experimental modification, both in vivo and by
means of tissue culture and explantation techniques. Molecular species
or mixtures may be added or subtracted at will under favourable
experimental conditions. Production of new substances can be sampled
and analysed. Hormones, vitamins, amino acids, inhibitors and other
molecular species may be added to this compartment either in vivo or
in vitro.
Insofar as overt morphological and biochemical differentiation is
concerned, experience almost overwhelmingly indicates that the cues to
a particular differentiation are mutually exclusive. Thus the cues which
drive the developing specific metabolism of a developing pigment cell
into its particular and exclusive pathways do not permit differentiation
at the same time (presumably in response to other cues) into a differentiation pattern appropriate to developing erythrocytes. Biochemically
the conversion of the differentiating cell's metabolism into a specific
synthetic pathway, such as melanoprotein synthesis, is not, insofar as
current observations indicate, compatible with massive haemoglobin
synthesis. Where the metabolic conversion is not as complete, stem or
precursor cells may still have open to them several distinct differentiative
pathways or may be capable of mild alterations of type. Such alterations
have been characterized by Weiss (1939), as modulations. Still, cells
capable of modulatory activity are not at once cartilage cells and
fibroblasts. There is a time interval of measurable extent between the
manifestation of two modulatory states.
The apparent uniqueness or 'one way drive' of differentiative activities
still awaits crucial experimental test. Grobstein (1959), has clearly
demarcated the problem. The uniqueness of differentiation in any
particular cell may be a function of metabolic cues from nucleus,
cytoplasm, micro-environment or all in mutual co-operation. In the
total absence of evidence concerning unique cues from nucleus or cytoplasm, there is some early evidence that the uniqueness of differentiating
tissue fabrics and of individual cells may be due in large part to cues
contained in the micro-environment. Moscona (1959), has reported
evidence of this nature in reaggregative phenomena, while studies on
cells from which ECM (Moscona, 1959, Extra Cellular Material) has been
CHARLES
Ε.
WILDE
they derive certain metabolites remains to be discussed. A microenvironment cogent to the processes of cellular differentiation must
subsume the totality of molecular species in the non-living immediate
environment and also those readily exchangeable between cells in the
vicinity or between cell and non-protoplasmic space. Thus cues may be
passed into the micro-environment from adjacent cells and thence to
the differentiating cell with or without intervening reactions in the
immediate non-protoplasmic milieu. The micro-environment is the most
convenient area for experimental modification, both in vivo and by
means of tissue culture and explantation techniques. Molecular species
or mixtures may be added or subtracted at will under favourable
experimental conditions. Production of new substances can be sampled
and analysed. Hormones, vitamins, amino acids, inhibitors and other
molecular species may be added to this compartment either in vivo or
in vitro.
Insofar as overt morphological and biochemical differentiation is
concerned, experience almost overwhelmingly indicates that the cues to
a particular differentiation are mutually exclusive. Thus the cues which
drive the developing specific metabolism of a developing pigment cell
into its particular and exclusive pathways do not permit differentiation
at the same time (presumably in response to other cues) into a differentiation pattern appropriate to developing erythrocytes. Biochemically
the conversion of the differentiating cell's metabolism into a specific
synthetic pathway, such as melanoprotein synthesis, is not, insofar as
current observations indicate, compatible with massive haemoglobin
synthesis. Where the metabolic conversion is not as complete, stem or
precursor cells may still have open to them several distinct differentiative
pathways or may be capable of mild alterations of type. Such alterations
have been characterized by Weiss (1939), as modulations. Still, cells
capable of modulatory activity are not at once cartilage cells and
fibroblasts. There is a time interval of measurable extent between the
manifestation of two modulatory states.
The apparent uniqueness or 'one way drive' of differentiative activities
still awaits crucial experimental test. Grobstein (1959), has clearly
demarcated the problem. The uniqueness of differentiation in any
particular cell may be a function of metabolic cues from nucleus,
cytoplasm, micro-environment or all in mutual co-operation. In the
total absence of evidence concerning unique cues from nucleus or cytoplasm, there is some early evidence that the uniqueness of differentiating
tissue fabrics and of individual cells may be due in large part to cues
contained in the micro-environment. Moscona (1959), has reported
evidence of this nature in reaggregative phenomena, while studies on
cells from which ECM (Moscona, 1959, Extra Cellular Material) has been