Limits...
Cell lineages and the logic of proliferative control.

Lander AD, Gokoffski KK, Wan FY, Nie Q, Calof AL - PLoS Biol. (2009)

Bottom Line: We begin by specifying performance objectives-what, precisely, is being controlled, and to what degree-and go on to calculate how well different types of feedback configurations, feedback sensitivities, and tissue architectures achieve control.Ultimately, we show that many features of the OE-the number of feedback loops, the cellular processes targeted by feedback, even the location of progenitor cells within the tissue-fit with expectations for the best possible control.In so doing, we also show that certain distinctions that are commonly drawn among cells and molecules-such as whether a cell is a stem cell or transit-amplifying cell, or whether a molecule is a growth inhibitor or stimulator-may be the consequences of control, and not a reflection of intrinsic differences in cellular or molecular character.

View Article: PubMed Central - PubMed

Affiliation: Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA. adlander@uci.edu

ABSTRACT
It is widely accepted that the growth and regeneration of tissues and organs is tightly controlled. Although experimental studies are beginning to reveal molecular mechanisms underlying such control, there is still very little known about the control strategies themselves. Here, we consider how secreted negative feedback factors ("chalones") may be used to control the output of multistage cell lineages, as exemplified by the actions of GDF11 and activin in a self-renewing neural tissue, the mammalian olfactory epithelium (OE). We begin by specifying performance objectives-what, precisely, is being controlled, and to what degree-and go on to calculate how well different types of feedback configurations, feedback sensitivities, and tissue architectures achieve control. Ultimately, we show that many features of the OE-the number of feedback loops, the cellular processes targeted by feedback, even the location of progenitor cells within the tissue-fit with expectations for the best possible control. In so doing, we also show that certain distinctions that are commonly drawn among cells and molecules-such as whether a cell is a stem cell or transit-amplifying cell, or whether a molecule is a growth inhibitor or stimulator-may be the consequences of control, and not a reflection of intrinsic differences in cellular or molecular character.

Show MeSH
Biological Pathways That Are Potential Targets of ControlLike metabolic, signaling, and gene expression pathways, cell lineages may be viewed as input–output pathways in which information or material flows through a series of defined elements (A–D) at rates controlled by measurable parameters (e.g., enzyme levels E1, E2, synthesis rates v1, v2, etc.). Unlike these other pathways, cell lineages are characterized by a potential for exponential expansion at most or all stages (parameters p0, p1, etc.). The impact of this difference on the strategies that may be used for tissue growth control has been little studied.
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pbio-1000015-g001: Biological Pathways That Are Potential Targets of ControlLike metabolic, signaling, and gene expression pathways, cell lineages may be viewed as input–output pathways in which information or material flows through a series of defined elements (A–D) at rates controlled by measurable parameters (e.g., enzyme levels E1, E2, synthesis rates v1, v2, etc.). Unlike these other pathways, cell lineages are characterized by a potential for exponential expansion at most or all stages (parameters p0, p1, etc.). The impact of this difference on the strategies that may be used for tissue growth control has been little studied.

Mentions: In recent years, increasing attention has been focused on the control challenges of biological networks, including those associated with metabolism, intracellular signaling, and gene regulation (e.g., [23–26]). Superficially, cell lineages look a great deal like these other kinds of pathways (Figure 1). Yet the components of lineages—cell stages—do not just transmit signals or material from one to another; they typically undergo autonomous, exponential expansion at the same time. This imparts a characteristic volatility to lineage dynamics that no doubt poses challenges for control. Given such challenges, it would not be surprising if the control of tissue and organ growth necessitates control strategies unlike those encountered elsewhere in biology. Here, we take steps toward identifying such strategies.


Cell lineages and the logic of proliferative control.

Lander AD, Gokoffski KK, Wan FY, Nie Q, Calof AL - PLoS Biol. (2009)

Biological Pathways That Are Potential Targets of ControlLike metabolic, signaling, and gene expression pathways, cell lineages may be viewed as input–output pathways in which information or material flows through a series of defined elements (A–D) at rates controlled by measurable parameters (e.g., enzyme levels E1, E2, synthesis rates v1, v2, etc.). Unlike these other pathways, cell lineages are characterized by a potential for exponential expansion at most or all stages (parameters p0, p1, etc.). The impact of this difference on the strategies that may be used for tissue growth control has been little studied.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2628408&req=5

pbio-1000015-g001: Biological Pathways That Are Potential Targets of ControlLike metabolic, signaling, and gene expression pathways, cell lineages may be viewed as input–output pathways in which information or material flows through a series of defined elements (A–D) at rates controlled by measurable parameters (e.g., enzyme levels E1, E2, synthesis rates v1, v2, etc.). Unlike these other pathways, cell lineages are characterized by a potential for exponential expansion at most or all stages (parameters p0, p1, etc.). The impact of this difference on the strategies that may be used for tissue growth control has been little studied.
Mentions: In recent years, increasing attention has been focused on the control challenges of biological networks, including those associated with metabolism, intracellular signaling, and gene regulation (e.g., [23–26]). Superficially, cell lineages look a great deal like these other kinds of pathways (Figure 1). Yet the components of lineages—cell stages—do not just transmit signals or material from one to another; they typically undergo autonomous, exponential expansion at the same time. This imparts a characteristic volatility to lineage dynamics that no doubt poses challenges for control. Given such challenges, it would not be surprising if the control of tissue and organ growth necessitates control strategies unlike those encountered elsewhere in biology. Here, we take steps toward identifying such strategies.

Bottom Line: We begin by specifying performance objectives-what, precisely, is being controlled, and to what degree-and go on to calculate how well different types of feedback configurations, feedback sensitivities, and tissue architectures achieve control.Ultimately, we show that many features of the OE-the number of feedback loops, the cellular processes targeted by feedback, even the location of progenitor cells within the tissue-fit with expectations for the best possible control.In so doing, we also show that certain distinctions that are commonly drawn among cells and molecules-such as whether a cell is a stem cell or transit-amplifying cell, or whether a molecule is a growth inhibitor or stimulator-may be the consequences of control, and not a reflection of intrinsic differences in cellular or molecular character.

View Article: PubMed Central - PubMed

Affiliation: Department of Developmental and Cell Biology, University of California, Irvine, Irvine, California, USA. adlander@uci.edu

ABSTRACT
It is widely accepted that the growth and regeneration of tissues and organs is tightly controlled. Although experimental studies are beginning to reveal molecular mechanisms underlying such control, there is still very little known about the control strategies themselves. Here, we consider how secreted negative feedback factors ("chalones") may be used to control the output of multistage cell lineages, as exemplified by the actions of GDF11 and activin in a self-renewing neural tissue, the mammalian olfactory epithelium (OE). We begin by specifying performance objectives-what, precisely, is being controlled, and to what degree-and go on to calculate how well different types of feedback configurations, feedback sensitivities, and tissue architectures achieve control. Ultimately, we show that many features of the OE-the number of feedback loops, the cellular processes targeted by feedback, even the location of progenitor cells within the tissue-fit with expectations for the best possible control. In so doing, we also show that certain distinctions that are commonly drawn among cells and molecules-such as whether a cell is a stem cell or transit-amplifying cell, or whether a molecule is a growth inhibitor or stimulator-may be the consequences of control, and not a reflection of intrinsic differences in cellular or molecular character.

Show MeSH