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. Author manuscript; available in PMC: 2018 Jul 17.

Published in final edited form as: Dev Biol. 2011 Dec 13;362(2):194–218. doi: 10.1016/j.ydbio.2011.12.009

Fig. 22 — Proposed model of intestinal epithelial cell lineage derivation. (A) Schematic representation of the gene networks operating within the intestinal epithelium to define the various epithelial cell lineages. Stem cells, S, give rise to short-lived Mix progenitors as they leave the stem cell zone and initiate differentiation. The initially equivalent daughters of Mix (DOM) each express low levels of Hes1, Atoh1, and Gfi1b. Depending on whether Hes1, Atoh1, or Gfi1b dominates in a DOM the cell will invoke a columnar, granulocytic, or brush cell lineage program, respectively. (B) In wild type epithelium, lateral inhibitory Notch signaling between the two equivalent DOMs breaks their symmetry leading to DOM_Notch and DOM_Delta states which usually give rise to Hes1- and Atoh1-expressing cells, respectively. Hes1-expressing cells become the columnar cell lineage progenitors, C₁. The Atoh1-expressing cells commence a granulocytic lineage program, G₁, and immediately commit to one of the granulocytic lineages through the interaction of various downstream factors including Neurog3 and Gfi1, leading to formation of a mucous, enteroendocrine, or a Paneth progenitor (M₁, E₁, or P₁). Alternatively, up regulation of Gfi1b in DOM_Delta represses Atoh1 and invokes the brush cell lineage program. (C) In the absence of Atoh1, lateral inhibition between DOMs gives rise to Hes1- and Gfi1b-expressing cells. As a result Atoh1⁻^/⁻ epithelium lacks granulocytic cell lineages, and contains an expanded brush cell population in addition to the columnar cell lineage. (D) In Notch-IC clones from Tamoxifen-treated Rosa26CreERT2^{/floxed-STOP-Notch-IC-Ires-EGFP} mice, Hes1 is over expressed due to the Notch-IC transgene, resulting in columnar cell lineage clones. Rarely, perhaps due to fluctuations in Hes1 levels allowing sufficient Gfi1b expression, a DOM invokes the brush cell lineage program.

Fig. 22 — Proposed model of intestinal epithelial cell lineage derivation. (A) Schematic representation of the gene networks operating within the intestinal epithelium to define the various epithelial cell lineages. Stem cells, S, give rise to short-lived Mix progenitors as they leave the stem cell zone and initiate differentiation. The initially equivalent daughters of Mix (DOM) each express low levels of Hes1, Atoh1, and Gfi1b. Depending on whether Hes1, Atoh1, or Gfi1b dominates in a DOM the cell will invoke a columnar, granulocytic, or brush cell lineage program, respectively. (B) In wild type epithelium, lateral inhibitory Notch signaling between the two equivalent DOMs breaks their symmetry leading to DOM_Notch and DOM_Delta states which usually give rise to Hes1- and Atoh1-expressing cells, respectively. Hes1-expressing cells become the columnar cell lineage progenitors, C₁. The Atoh1-expressing cells commence a granulocytic lineage program, G₁, and immediately commit to one of the granulocytic lineages through the interaction of various downstream factors including Neurog3 and Gfi1, leading to formation of a mucous, enteroendocrine, or a Paneth progenitor (M₁, E₁, or P₁). Alternatively, up regulation of Gfi1b in DOM_Delta represses Atoh1 and invokes the brush cell lineage program. (C) In the absence of Atoh1, lateral inhibition between DOMs gives rise to Hes1- and Gfi1b-expressing cells. As a result Atoh1⁻^/⁻ epithelium lacks granulocytic cell lineages, and contains an expanded brush cell population in addition to the columnar cell lineage. (D) In Notch-IC clones from Tamoxifen-treated Rosa26CreERT2^{/floxed-STOP-Notch-IC-Ires-EGFP} mice, Hes1 is over expressed due to the Notch-IC transgene, resulting in columnar cell lineage clones. Rarely, perhaps due to fluctuations in Hes1 levels allowing sufficient Gfi1b expression, a DOM invokes the brush cell lineage program.