The analysis of Pax9 expression in compound mutants indicates that both spatial expansion and upregulation of Pax9 expression account for its compensatory function during sclerotome development in the absence of Pax1. In Pax1/Pax9 double homozygous mutants, formation

The vertebrate body is supported by the vertebral column, a series of segmental skeletal elements that provide both stability and mobility. The development of the axial skeleton is a multistep process starting with the formation of somites from the unsegmented paraxial mesoderm on both sides of the neural tube. Shortly after formation, the somites compartmentalise to generate dermomyotomes and sclerotomes, the latter forming skeletal elements of the vertebral column and ribs. Vertebral column development requires the co-ordination of a series of cellular events. These include de-epithelialization of somites, proliferation and migration of sclerotomal cells, and establishment of anteroposterior polarity of the sclerotome (reviewed in Keynes and Stern, 1988; Christ and Wilting, 1992; Christ and Ordahl, 1995). In mammals, a single vertebra is composed of a variety of components that perform different functions, depending on the level of the body axis. Thus, a finetuned regulation is required to co-ordinate the prepatterning of individual skeletal elements by region-specific mesenchymal growth and condensations that are finally replaced by cartilage and bone. Although in the recent years much progress has been made in the understanding of somite patterning and sclerotome formation (Tajbakhsh and Spörle, 1998), most aspects of the genetic control that regulates the complex development from the sclerotomal mesenchymes to the vertebral column remain to be elucidated. Pax1 and Pax9 form one group within the family of nine vertebrate Pax genes, which are unified by the presence of the paired box that encodes a DNA-binding domain (Walther et al., 1991; Noll, 1993). Analyses of mouse mutants of all Pax genes have demonstrated multiple roles in the genetic control of mammalian organogenesis (reviewed in Dahl et al., 1997). The 128 amino acid long DNA-binding paired domains of Pax1 and Pax9 are almost identical (98%). DNA-binding studies have shown that the e5 site, a DNA element present in the 5399 Development 126, 5399-5408 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 DEV4240