Integrating and Integrating and Controlling Controlling SignalsSignals

By Kimmie Bui

Cells change in response to Cells change in response to signals during and after signals during and after developmentdevelopment

In many circumstances, responses depends on the ability to receive cells to integrate multiple signals and to control the availability of active cells.

Competence Depends on Properties of Cells that enable them to respond to Inductive Signals enable them to respond to Inductive Signals.

Competence- is the ability to respond to various inductive signals.

The reception of one signal may make cells competent to receive another.

Ex: After one part of the liver is damaged Ex: After one part of the liver is damaged or surgically removed, increased amounts or surgically removed, increased amounts of two signals, tumor necrosis factor of two signals, tumor necrosis factor (TNF) and interleukin-6 (IL-6) are (TNF) and interleukin-6 (IL-6) are produced as part of the response to liver produced as part of the response to liver damage. These two signals cause damage. These two signals cause hepatocyte, which will increase their hepatocyte, which will increase their production of transcription factors (NF-kB, production of transcription factors (NF-kB, Stat3, API and CEBP) but does not Stat3, API and CEBP) but does not provide.provide.

Liver regeneration is important after it has been damaged or poisoned. The unregulated growth could lead to cancer.

Some signals can Induce Some signals can Induce Diverse Cellular ResponseDiverse Cellular Response Several mechanisms for producing diverse cellular

response to a particular signaling molecule seem possible in principle.

The strength or duration of the signal governs the nature of the responses

The pathway downstream of the receptor is not really the same in different cell type.

Converging inputs from other pathways modify the response to the signal.

Limb Development Depends Limb Development Depends on the Integration of Multiple on the Integration of Multiple Extracellular Signal GradientsExtracellular Signal Gradients Vertebrate limbs grow from small “buds”

composed of an inner mass of mesoderm cells surrounded by a sheath of ectoderm.

There are three dimensions to a limb.

-Anterior/posterior (thumb to little finger).

-Dorsal/ventral (palm verses back of hand).

-Proximal/distal (shoulder to fingers).

Fibroblast Growth Factor Fibroblast Growth Factor (FGF10) - signal comes from (FGF10) - signal comes from the mesoderm in specific the mesoderm in specific regions of the embryo flankregions of the embryo flankFGF10- is a local region of surface

ectoderm that becomes the signaling center.Apical Ectodermal Ridge (AER)- is at the

tip of emerging limb bud.Both of these drive persistent division of

mesoderm cells and continue limb growth.

Signals are buffered by the Signals are buffered by the Intracellular and Extracellular Intracellular and Extracellular AntagonistAntagonist Many organisms experience a wide variation in

their environment and must adapt or die. Inducible Antagonist-signal induces the

transcription of genes in the receiving cells. Anatogonist Not Induced by signal secreted

antagonist comes from the opposite direction; it will block the action of the signal even in cells receiving above-threshold amounts.

Conclusion:Conclusion:

In liver regeneration, early signals change cells into a primed state in which they are competent to respond to subsequent signals that causes growth and mitosis.

At least one signaling protein acts along each axis of the developing limb bud. Cells responds to many combination of signals, and the signals reinforce the production of other signals to coordinate growth and patterning in three-dimension.

-Include intracellular and secreted proteins whose -Include intracellular and secreted proteins whose production is induced by a particular signal. The production is induced by a particular signal. The antagonist protein then feeds back; opposing the antagonist protein then feeds back; opposing the ongoing action of the signal. Inducible antagonist ongoing action of the signal. Inducible antagonist provides buffering in most signaling pathways to provides buffering in most signaling pathways to compensate for excess or inadequate signals.compensate for excess or inadequate signals.

-Signals can also be controlled by antagonist that -Signals can also be controlled by antagonist that are not induced by the signal itself. By binding to are not induced by the signal itself. By binding to signals, these antagonists prevent the signals from signals, these antagonists prevent the signals from binding to their specific receptors and activating binding to their specific receptors and activating them.them.

Questions?Questions?