468
CLIFFORD GROBSTEIN
immediate future is to understand the relationships and interactions
within organ cultures which favor differentiation, in the hope that they
may provide clues to maintaining differentiated cells in the simpler
conditions of cell culture.
This leads to the second focus of differentiative studies in vitro—
understanding of the process itself and of the environmental factors,
chemical and cellular, which govern it. The latter, to which culture
techniques seem to provide the ideal approach, is the subject of much of
what follows. A few general remarks, however, may prove a useful
preliminary. We have not yet been able to identify the critical processes,
in a control sense, which go on within a cell as it differentiates, nor to
say how these processes are cued or controlled from the outside. Until
this is done we are forced to characterize the process by its consequences.
We may assume some such time course as is diagrammed in Fig. 1. The
Period
Specialized structure
and function
Specific synthesis
Criteria
Morphological
functional
Chemical
Covert stabilization
Developmental
Course of differentiation
Induction
Time
FIG. 1.
curve represents differentiative level, by whatever criteria it may be
best expressed, plotted against time. Three phases are distinguished:
covert stabilization, specific synthesis, and structural and functional
specialization. It is intended to suggest, and the evidence indicates,
that these phases begin in the order indicated. It is not intended to
suggest that the phases are exclusive or strictly sequential. Rather the
phases probably are cumulative, stabilization extending into the period
of synthesis, specific synthesis continuing during function, etc. Questions
of the following sort immediately arise. How real is the period of covert
stabilization—is it truly separable from the period of specific synthesis
or is it an artifact due to restricted sensitivity of methods of detection?
If covert stabilization is real, how is it initiated and is its mechanism
CLIFFORD GROBSTEIN
immediate future is to understand the relationships and interactions
within organ cultures which favor differentiation, in the hope that they
may provide clues to maintaining differentiated cells in the simpler
conditions of cell culture.
This leads to the second focus of differentiative studies in vitro—
understanding of the process itself and of the environmental factors,
chemical and cellular, which govern it. The latter, to which culture
techniques seem to provide the ideal approach, is the subject of much of
what follows. A few general remarks, however, may prove a useful
preliminary. We have not yet been able to identify the critical processes,
in a control sense, which go on within a cell as it differentiates, nor to
say how these processes are cued or controlled from the outside. Until
this is done we are forced to characterize the process by its consequences.
We may assume some such time course as is diagrammed in Fig. 1. The
Period
Specialized structure
and function
Specific synthesis
Criteria
Morphological
functional
Chemical
Covert stabilization
Developmental
Course of differentiation
Induction
Time
FIG. 1.
curve represents differentiative level, by whatever criteria it may be
best expressed, plotted against time. Three phases are distinguished:
covert stabilization, specific synthesis, and structural and functional
specialization. It is intended to suggest, and the evidence indicates,
that these phases begin in the order indicated. It is not intended to
suggest that the phases are exclusive or strictly sequential. Rather the
phases probably are cumulative, stabilization extending into the period
of synthesis, specific synthesis continuing during function, etc. Questions
of the following sort immediately arise. How real is the period of covert
stabilization—is it truly separable from the period of specific synthesis
or is it an artifact due to restricted sensitivity of methods of detection?
If covert stabilization is real, how is it initiated and is its mechanism