Fig. 7. Schematic model for hindbrain segmentation in wild-type and Krox20^–/– embryos. (A) Wild-type situation. At the 1-5 s stages, Krox20 is activated in a few scattered cells in prospective r3, and in a more coherent group of cells in prospective r5 (light blue circles). Hoxb1 (green) and Mafb/kr (Kr) (orange), and the Hoxa2 (r2) (yellow) enhancer are also activated. Additional cells are subsequently recruited to express Krox20, probably by a non cell-autonomous autoactivation process (light blue arrows). At the 8-10 s stage, prospective r3 and r5 now express Krox20 homogeneously, and continue to expand by cell recruitment at the expense of r2/r4 (for r3) and of r6 (for r5). In addition, an autoregulatory loop (curved arrows) leads to enhancement of Krox20 expression, presumably in a cell-autonomous manner. Krox20 expression in these cells leads to acquisition of r3/r5 molecular identity (Epha4, Hoxa2-r3/r5 enhancer activation) and repression of even-numbered rhombomere molecular identity (e.g. Hoxb1, Hoxa2-r2 enhancer repression). At the 12 s stage, r3 and r5 express Krox20 at high levels (dark blue) and have acquired r3/r5 identity, including cell mingling properties. This leads to the sorting of even- and odd-numbered rhombomere cells, and sharpening of gene expression limits. At the 20-25 s stage, boundaries are morphologically conspicuous. (B) In Krox20-null mutants, at the 1-5 s stages, early activation of Krox20 occurs normally (light blue circles). However, the Krox20-expressing territories do not expand, because of defective cell recruitment based on non cell-autonomous autoregulation. At the 8-10 s stage, Krox20-expressing cells are still scattered. They have acquired even-numbered rhombomere identity and are incorporated into adjacent even-numbered territories, namely r2 and r4 for cells that should belong to r3, and r6 for cells that should give rise to r5. At the 12 s stage, Krox20 gene expression is not maintained in these cells, owing to impaired cell autonomous autoregulation. Finally, at the 20-25 s stage, cell death in the even-numbered rhombomeres leads to a significant size reduction of the hindbrain.