Developmental expression of Dkk1-3 and Mmp9 and apoptosis in cranial base of mice

Abstract

The Dickkopf (Dkk) family and Mmp9 are important for apoptosis and a number of other developmental processes. However, little is known about their roles in the development of cranial base, which is an important structure for coordinated development and growth of the craniofacial skeletons. In order to establish whether and in what way these genes are involved in cranial base development, we examined their expression patterns and cell apoptosis. Dkk1 was first seen in the perichondral mesenchyme in restricted domains from E14, and later in the migrating mesenchymal cells within the cartilage. Thereafter, it was widespread throughout the bones of the cranial base. The expression was downregulated in postnatal stages. Dkk2 was localized in the perichondral mesenchyme outlining the anterior cranial base in embryogenesis. Dkk3 was mainly detected in the occipital-vertebral joint at E13 and E14. Mmp9 transcripts were clustered in the inner layer of perichondral mesenchyme, juxtaposed with the terminally differentiated hypertrophic chondrocytes from E14. Later Mmp9-expressing cells were found at the sites of chondrocyte apoptosis. This was particularly clear at the distal ends of the synchondroses. These data indicate that Mmp9 regulates skeletogenesis in cranial base in a manner that is largely similar to that of the appendicular skeletons. Expression of Dkks suggests other roles that remain to be defined.

Secreted and Transmembrane Wnt Inhibitors and Activators

“…Given the paramount role that Wnts play during embryonic development, it is not surprising that one main function of Dkks is to control cell fate in vertebrates as they show highly regionalized expression (Grotewold et al 1999;Monaghan et al 1999;Hashimoto et al 2000;Shinya et al 2000;Chapman et al 2004;Diep et al 2004;Idkowiak et al 2004;Fjeld et al 2005;Nie 2005;Nie et al 2005). Dkk1, -2, and -3 mouse mutants are available and a summary of their phenotypes is presented in Table 1.…”

Update on Wnt signaling in bone cell biology and bone disease

“…The Dickkopf factors (Dkk1–4) have differing expression patterns during embryonic and postnatal development (Nie et al, 2005; Witte et al, 2009). Dkks bind and sequester the Lrp5/6 and Krm1/2 membrane complex to inhibit Wnt activity.…”

TGFβ regulates epithelial-mesenchymal interactions through WNT signaling activity to control muscle development in the soft palate

“…Using the mouse model, we explored how loss of TGFβ signaling in epithelial cells results in a failure of muscle development and found that TGFβ-controlled WNT-β-catenin signaling activity is crucial for muscle formation. Previous studies indicated that DKK1 and DKK4 can inhibit WNT-β-catenin signaling (Kawano and Kypta, 2003;Nie et al, 2005;Semënov et al, 2001). Dkk1 knockout mice exhibit severe craniofacial deformities and embryonic lethality before palatal development (Mukhopadhyay et al, 2001).…”