Fig. 3.
Fig. 3. Relative levels of Notch expression determine sequential cell fates. (A) Lateral signaling among a group of equipotent progenitors permits the generation of cells of distinct lineages in response to inductive signals. When exposed to signal A, cells expressing less Notch and more ligand (L) respond by adopting the primary cell fate A; adjacent cells expressing more Notch (N) are inhibited from adopting fate A, but remain competent to respond to subsequent signals. Among these remaining progenitors, differential expression of Notch again determines which cells will respond to inductive signal B: those expressing less Notch adopt fate B, whereas those expressing more are again inhibited from differentiating. Differential Notch and DSL ligand expression among the remaining progenitors at each subsequent step similarly restricts the number of cells responding to signals C and D. Thus, from a group of originally equipotent progenitors, cells of multiple distinct lineages are established, and some uncommitted progenitors are maintained. (B) Notch functions through successive cell divisions to influence the numbers and types of cells generated from a multipotent progenitor. Normal Notch expression (left panel) allows the A/B progenitor to give rise to cells of four distinct lineages; at each cell division, the daughter cell expressing less Notch adopts the primary fate, whereas the cell expressing more adopts the alternative secondary fate. The A/B progenitor gives rise to A (primary) and B (secondary) cells; progeny of type A cells expressing less Notch subsequently adopt the primary fate A1, whereas those expressing more Notch adopt the secondary fate A2; the same occurs for type B cells. The result is balanced production of cells of all four lineages. When Notch activity is dysregulated, the result is overproduction of one cell type at the expense of another. With loss of Notch function (middle panel), all cells adopt the primary fates resulting in production of only A1 cells. With increased Notch activity (right panel), daughter cells adopt the secondary fates, generating only B2 cells.

Relative levels of Notch expression determine sequential cell fates. (A) Lateral signaling among a group of equipotent progenitors permits the generation of cells of distinct lineages in response to inductive signals. When exposed to signal A, cells expressing less Notch and more ligand (L) respond by adopting the primary cell fate A; adjacent cells expressing more Notch (N) are inhibited from adopting fate A, but remain competent to respond to subsequent signals. Among these remaining progenitors, differential expression of Notch again determines which cells will respond to inductive signal B: those expressing less Notch adopt fate B, whereas those expressing more are again inhibited from differentiating. Differential Notch and DSL ligand expression among the remaining progenitors at each subsequent step similarly restricts the number of cells responding to signals C and D. Thus, from a group of originally equipotent progenitors, cells of multiple distinct lineages are established, and some uncommitted progenitors are maintained. (B) Notch functions through successive cell divisions to influence the numbers and types of cells generated from a multipotent progenitor. Normal Notch expression (left panel) allows the A/B progenitor to give rise to cells of four distinct lineages; at each cell division, the daughter cell expressing less Notch adopts the primary fate, whereas the cell expressing more adopts the alternative secondary fate. The A/B progenitor gives rise to A (primary) and B (secondary) cells; progeny of type A cells expressing less Notch subsequently adopt the primary fate A1, whereas those expressing more Notch adopt the secondary fate A2; the same occurs for type B cells. The result is balanced production of cells of all four lineages. When Notch activity is dysregulated, the result is overproduction of one cell type at the expense of another. With loss of Notch function (middle panel), all cells adopt the primary fates resulting in production of only A1 cells. With increased Notch activity (right panel), daughter cells adopt the secondary fates, generating only B2 cells.

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