269
Digestive and Respiratory System
FIGURE 18.6 Regulation of respiratory progenitor induction and tracheoesophageal separation in Xenopus. (A) Schematic of a
cross-section through the NF32-NF35 Xenopus foregut. Bi-directional signaling between the lateral plate mesoderm (tan) and the
endoderm (blue, red) involving RA, HH, Wnt, and BMP governs induction of Nkx2–1 respiratory progenitors (red) in the ventral foregut. Notochord indicated in gray, which expresses the BMP antagonist Noggin. A ventral (high) to dorsal (low) gradient
of Wnt/β-Catenin and BMP/pSmad1/5/9 activity exists along the foregut dorsal-ventral axis. (B-C) Immunostaining of NF34/35
X. laevis foregut sections for the indicated color-coded factors. In B, FoxF1 (green) is expressed in lateral plate mesoderm; Sox2
(blue) in dorsal esophageal progenitors; Nkx2–1 (red) in ventral respiratory progenitors. In C, Aldh1a2 (green) is expressed in lateral
plate mesoderm; phosphorylated Smad1/5/9 (pSmad, red) in ventral endoderm and mesoderm. (D-F) In situ hybridization of NF34/35
X. laevis foregut sections of shh (expressed in both dorsal and ventral endoderm) and wnt2b, bmp4 (both expressed in ventral lateral
plate mesoderm). (G) Schematic of tracheal-esophageal separation and morphogenesis in Xenopus, from stages NF35 to NF44. Key
events are diagrammed in the section schematics below the separating foregut tube cartoons. By NF35, medial constriction is progressing; subsequently, from NF36–NF40, a transient epithelial septum (purple) forms wherein midline epithelial cells (MECs) touch
and down-regulate their apical membrane surface proteins. Separation of the dorsal esophagus (e) and ventral trachea (t) involves
epithelial as well as extracellular matrix (ECM) remodeling and laminin basement membrane breakdown adjacent to the epithelial
septum. (H) Immunostaining of NF41 X. laevis foregut section, showing Foxf1+ mesoderm cells (green) between the separating dorsal esophagus (e) and ventral trachea (t).
Digestive and Respiratory System
FIGURE 18.6 Regulation of respiratory progenitor induction and tracheoesophageal separation in Xenopus. (A) Schematic of a
cross-section through the NF32-NF35 Xenopus foregut. Bi-directional signaling between the lateral plate mesoderm (tan) and the
endoderm (blue, red) involving RA, HH, Wnt, and BMP governs induction of Nkx2–1 respiratory progenitors (red) in the ventral foregut. Notochord indicated in gray, which expresses the BMP antagonist Noggin. A ventral (high) to dorsal (low) gradient
of Wnt/β-Catenin and BMP/pSmad1/5/9 activity exists along the foregut dorsal-ventral axis. (B-C) Immunostaining of NF34/35
X. laevis foregut sections for the indicated color-coded factors. In B, FoxF1 (green) is expressed in lateral plate mesoderm; Sox2
(blue) in dorsal esophageal progenitors; Nkx2–1 (red) in ventral respiratory progenitors. In C, Aldh1a2 (green) is expressed in lateral
plate mesoderm; phosphorylated Smad1/5/9 (pSmad, red) in ventral endoderm and mesoderm. (D-F) In situ hybridization of NF34/35
X. laevis foregut sections of shh (expressed in both dorsal and ventral endoderm) and wnt2b, bmp4 (both expressed in ventral lateral
plate mesoderm). (G) Schematic of tracheal-esophageal separation and morphogenesis in Xenopus, from stages NF35 to NF44. Key
events are diagrammed in the section schematics below the separating foregut tube cartoons. By NF35, medial constriction is progressing; subsequently, from NF36–NF40, a transient epithelial septum (purple) forms wherein midline epithelial cells (MECs) touch
and down-regulate their apical membrane surface proteins. Separation of the dorsal esophagus (e) and ventral trachea (t) involves
epithelial as well as extracellular matrix (ECM) remodeling and laminin basement membrane breakdown adjacent to the epithelial
septum. (H) Immunostaining of NF41 X. laevis foregut section, showing Foxf1+ mesoderm cells (green) between the separating dorsal esophagus (e) and ventral trachea (t).
