Exclusion is spreading

Stretch but don’t follow s slow-twitch muscle cells migrate through fast-twitch muscle precursor cells, they act as morphogenesis tutors, according to Clarissa Henry and Sharon Amacher (University of California, Berkeley, CA). Fast-twitch muscle cells in zebrafish start off life as round blobs but must undergo anterio-posterior elongation to become functional myofibers. Henry and Amacher had noticed that this elongation process spreads in a medial-to-lateral wave, i.e., cells near the midline change shape first. The authors first established that elongation required Hedgehog signaling. Transplantation experiments showed, however, that this effect was indirect. To restore fasttwitch elongation in a Hedgehogsignaling mutant, the critical ingredient was wild-type slow-twitch cells not wild-type fast-twitch cells. In response to the Hedgehog signal, transplanted slow-twitch cells extended across the anterior–posterior width of a somite and migrated outwards from the notochord. Fasttwitch cells in their wake elongated. The effect could be relayed to other A Exclusion is spreading llelic exclusion simplifies the problem of immune recognition. It ensures that each B cell makes antibodies that recognize only one target because, once the DNA of a single immunoglobulin allele has rearranged to form a functional gene, the other allele is prevented from rearranging. Now Esther Roldán, Jane Skok (University College London, UK), and colleagues find that allele exclusion may rely on putting different parts of the unrearranged gene too far from each other to allow rearrangement. Rearrangement is only possible in such huge loci because of DNA contraction and (as shown here) looping that juxtaposes distant DNA sites. Skok and colleagues now show that successful rearrangement is immediately followed by decontraction of the unrearranged allele. Proximal variable (V) regions are still within reach of the rearrangement apparatus, but the products of these rearrangements are disfavored later because they pair poorly with immunoglobulin light chains and usually fail to induce positive selection of cells. There is a backup mechanism for allele exclusion. Coincident with decontraction, the unrearranged allele is also recruited to repressive centromeric domains. But Skok says she thinks decontraction “is the most important factor. Decontraction seems to be irreversible and immediate, whereas recruitment is reversible.”