Fig. 8. Model for NSM specification in the sea urchin embryos. (A) During the first Notch signal, the blastula stage (seventh to ninth cleavage) embryo expresses LvNotch (blue) and Fringe (orange) on the membranes of all cells of the embryo. Micromeres (pink) express the LvDelta protein (green arrows) and signal to adjacent macromeres (light blue), specifying pigment cells and blastocoelar cells. LvFringe is necessary for Delta to activate the LvNotch receptor in the macromere lineage. (B) After LvNotch signals in the macromere lineage, the receptor is cleared from the presumptive NSM territory and presumptive endoderm cells begin to express high levels of apical Notch. The presumptive NSM expresses apical LvNumb (red), partially overlapping with LvNotch expression at the boundary of the territory. LvNumb works with LvNotch, either directly or synergistically, to specify pigment and blastocoelar cells at this time. (C) During the second Notch signal, the micromeres have ingressed as PMCs and no longer express Delta. Delta is expressed in the presumptive NSM where they signal to Notch to specify blastocoelar cells and muscle cells (double headed green arrow). Delta may also activate Notch signaling in neighboring cells (green arrows). Similar to the first signal, Delta requires LvFringe to activate Notch signaling. In addition, LvNumb is necessary for specification of blastocoelar cells and muscle cells in the NSM, and perhaps it is necessary in neighboring cells as well. Notch signaling also activates a secondary signal that is necessary for some aspect of endoderm specification (black arrows). (D) By gastrula stage, LvDelta is no longer expressed. However, LvNotch is apically expressed on the dorsal side of the archenteron and LvNumb is apically expressed in the NSM territory (light blue) and the archenteron. LvFringe is not expressed in the archenteron. We speculate that these expression patterns suggest a role for LvNotch and LvNumb in later aspects of NSM and gut specification. It is possible that an as yet unidentified Notch ligand, Serrate, which cannot activate LvNotch in the presence of LvFringe, activates LvNotch at this time.