Segmental structures in vertebrates (the ribs, for example) develop from embryonic structures called somites - blocks of mesodermal cells that periodically bud off from the unsegmented presomitic mesoderm (PSM). Somite formation and the establishment of their rostro-caudal pattern require the transcription factor Mesp2. Now, Morimoto and colleagues reveal that negative regulation of Mesp2 by Ripply2, a putative transcriptional co-repressor, is required to establish rostro-caudal patterning within mouse somites (see ). Expression of Ripply2, the researchers report, is downregulated in Mesp2-null mice. Furthermore, Mesp2 binds to the Ripply2gene enhancer, indicating that Ripply2 is a direct target of Mesp2. Unexpectedly, given that Mesp2-null embryos fail to segment and have an extended caudal compartment in their PSM, Ripply2-null embryos have a rostralized phenotype because of prolonged Mesp2 expression. This and other findings suggest that Mesp2 activates Ripply2 but that Ripply2 negatively regulates Mesp2. This negative-feedback loop, the authors propose, is an essential component of the regulatory network that establishes rostro-caudal patterning within somites.
