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Fig. 4. Model for an asymmetrically dividing multipotent progenitor. A
single multipotent progenitor (large oval) is shown at several different time
points during development. The progenitor divides asymmetrically to `self
renew' and to generate a sequence of postmitotic progeny (small ovals), each
with a different temporal identity (represented by the different colours).
Within the progenitor, a temporal series timer (crescent) regulates the
activity of switching factors with time and thus the frequency of the
transitions (indicated by a sweeping arrow) between different progenitor TTFs
(A 
B C D E). The core of the temporal series timer
would be progenitor-intrinsic and could include both oscillatory and
hourglass-like elements (reviewed by
Pourquie, 1998;
Rensing et al., 2001).
Cross-regulatory repressions between some progenitor TTFs can promote these
transitions (lines above letters indicate a selection of possible
interactions), which may occur after one or many intervening cell cycles.
Transient expression of progenitor TTFs can induce long-lasting changes in the
expression pattern of a set of target genes - the progenitor competence
factors. These, in turn, can modify several properties of the progenitors,
including their ability to respond to later progenitor TTFs in the sequence.
Progenitor TTFs also function, in combination with progenitor competence
factors, to regulate the postmitotic TTFs (1, 2, 3, 4 and 5) that define the
temporal identity of postmitotic progeny. Temporal identities can be
stabilised by cross-regulatory interactions between the postmitotic TTFs
(lines between numbers indicate a selection of possible repressions). Possible
mechanisms for transmitting and transducing progenitor temporal information
into the temporal identity of postmitotic daughter cells are discussed in the
main text. For clarity, only one linear progenitor sequence (branch) is shown
and intermediate progenitors are omitted. However, the main features of this
general model also apply to progenitor lineages with more than one branch,
such as those in the cerebral cortex and haematopoietic system.
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