Pax-1, a regulator of sclerotome development is induced by notochord and floor plate signals in avian embryos.

in Anatomy & Embryology (1995), 191(4), 297-310

Pax-1 encodes for a DNA-binding transcriptional activator that was originally discovered in murine embryos using a probe from the Drosophila paired-box-containing gene, gooseberry-distal. We have cloned ... [more ▼]

Pax-1 encodes for a DNA-binding transcriptional activator that was originally discovered in murine embryos using a probe from the Drosophila paired-box-containing gene, gooseberry-distal. We have cloned the avian Pax-1 gene as a basis for experimental studies of the induction of Pax-1 in the paraxial mesoderm. The amino acid sequence of the paired-domain is exactly the same in the quail and mouse, whereas outside the paired-domain there is 61% homology. Starting at about the eight-somite stage, quail Pax-1 is expressed in the paraxial mesoderm in a craniocaudal sequence. The unsegmented paraxial mesoderm and the two most recently formed somites do not express Pax-1. In the epithelial somite, the somitocoele cells and the cells of the ventral two-thirds of the epithelial wall are positive. As soon as the sclerotome is formed, only a subset of sclerotome cells expresses Pax-1. These are the cells that migrate towards the notochord to form the perinotochordal tube. Expression then becomes restricted to the intervertebral discs, the perichondrium of the vertebral bodies and the connective tissue surrounding the spinal ganglia. Additional expression domains are found in the scapula and the pelvic region, distinct areas of the head, and the epithelium of the second to the fourth visceral pouch. In later stages the thymus is positive. In vitro and in vivo experiments show that the notochord induces Pax-1 in the paraxial mesoderm, but limb bud mesoderm is not competent to respond to notochordal signals. Floor plate is also capable of inducing Pax-1 expression in sclerotome cells. Our studies show that in competent cells of the paraxial mesoderm, Pax-1 is a mediator of signals emanating from the notochord and the floor plate. [less ▲]

A new Pax gene, Pax-9, maps to mouse chromosome 12.

in Mammalian Genome (1993), 4(7), 354-8

Members of the Pax gene family have recently been shown to play important roles in mouse embryogenesis. Of eight so far characterized Pax genes, three have been associated with mouse developmental mutants ... [more ▼]

Members of the Pax gene family have recently been shown to play important roles in mouse embryogenesis. Of eight so far characterized Pax genes, three have been associated with mouse developmental mutants. Here we report the cloning of a new Pax gene, Pax-9. Most of the DNA sequence encoding the highly conserved paired domain has been determined and compared with previously known paired domains. This comparison classifies Pax-9 as a member of the same subgroup as Pax-1/undulated. By analysis of the segregation of a Pax-9 restriction fragment length polymorphism and a large number of simple sequence length polymorphisms in an interspecific C57BL/6 x Mus musculus mollosinus backcross, Pax-9 was mapped close to the D12Nds1 locus on the proximal part of Chromosome (Chr) 12. [less ▲]

A role for Pax-1 as a mediator of notochordal signals during the dorsoventral specification of vertebrae.

in Development (1993), 119(3), 649-60

The notochord plays an important role in the differentiation of the paraxial mesoderm and the neural tube. We have analyzed the role of the notochord in somite differentiation and subsequent formation of ... [more ▼]

The notochord plays an important role in the differentiation of the paraxial mesoderm and the neural tube. We have analyzed the role of the notochord in somite differentiation and subsequent formation of the vertebral column using a mouse mutant, Danforth's short-tail (Sd). In this mutant, the skeletal phenotype is most probably a result of degeneration and subsequent loss of the notochord. The Sd gene is known to interact with undulated (un), a sclerotome mutant. Double mutants between Sd and un alleles show an increase in the severity of the defects, mainly in the ventral parts of the vertebrae. We also show that part of the Sd phenotype is strikingly similar to that of the un alleles. As un is known to be caused by a mutation in the Pax-1 gene, we analyzed Pax-1 expression in Sd embryos. In Sd embryos, Pax-1 expression is reduced, providing a potential molecular basis for the genetic interaction observed. A complete loss of Pax-1 expression in morphologically intact mesenchyme was found in the lower thoracic-lumbar region, which is phenotypically very similar to the corresponding region in a Pax-1 null mutant, Undulated short-tail. The sclerotome developmental abnormalities in Sd coincide closely, both in time and space, with notochordal changes, as determined by whole-mount T antibody staining. These findings indicate that an intact notochord is necessary for normal Pax-1 expression in sclerotome cells, which is in turn required for the formation of the ventral parts of the vertebrae. The observed correlation among structural changes of the notochord, Pax-1 expression levels and skeletal phenotypes, suggests that Pax-1 might be an intrinsic mediator of notochordal signals during the dorsoventral specification of vertebrae. [less ▲]