The cohesin complex ensures accurate sister chromatid segregation during cell division but it also seems to play an important role in development. For example, mutations in several cohesin components are associated with the human developmental disorder Cornelia de Lange syndrome (CdLS). Until now, there has been no animal model for this syndrome but, on p. 3191, Zhang and co-workers report that mice lacking the cohesin regulatory protein PDS5B are born with developmental abnormalities reminiscent of CdLS. Pds5B-deficient mice, like people with CdLS, exhibit abnormal skeletal patterning, heart defects and cleft palates, they report. Unexpectedly, however, the researchers did not find any chromosome cohesion defects in Pds5B-/- cells. Furthermore, they detected high PDS5B expression in post-mitotic neurons of wild-type mice, identified a DNA-binding domain in mouse PDS5B and showed that the protein localizes to the nucleolus. Overall, these results suggest that PDS5B and the cohesin complex might regulate multiple aspects of organogenesis by regulating developmental gene expression rather than chromosome dynamics.