Impaired meningeal development in association with apical expansion of calvarial bone osteogenesis in the Foxc1 mutant

Abstract

Loss of function of the mouse forkhead/winged helix transcription factor Foxc1 induces congenital hydrocephalus and impaired skull bone development due to failure of apical expansion of the bone. In this study we investigated meningeal development in the congenital hydrocephalus ( ch ) mouse with spontaneous loss of function mutant of Foxc1 , around the period of initiation of skull bone apical expansion. In situ hybridization of Runx2 revealed active apical expansion of the frontal bone begins between embryonic day 13.5 and embryonic day 14.5 in the wild type, whereas expansion was inhibited in the mutant. Ultrastructural analysis revealed that three layers of the meninges begin to develop at E13.5 in the basolateral site of the head and subsequently progress to the apex in wild type. In ch homozygotes, although three layers were recognized at first at the basolateral site, cell morphology and structure of the layers became abnormal except for the pia mater, and arachnoidal and dural cells never differentiated in the apex. We identified meningeal markers for each layer and found that their expression was down-regulated in the mutant arachnoid and dura maters. These results suggest that there is a close association between meningeal development and the apical growth of the skull bones.

Wnt5a can both activate and repress Wnt/β-catenin signaling during mouse embryonic development

“…Whereas Wnt/b-catenin signaling therefore appears to be required for bone formation, earlier activation of the pathway might result in the prolonged maintenance of a mesenchymal progenitor state. Although at present we have no proof that in tetO-Wnt5a;R26rtTA double-transgenic animals the increase in b-catenin/TCF signaling in the dura mater at E14.5 and E16.5 is directly responsible for the reduced bone formation observed at birth, it is generally well accepted that the dura mater affects osteogenesis in the overlying calvarial mesenchyme through the secretion of paracrine growth factors Spector et al, 2002;Vivatbutsiri et al, 2008). We therefore hypothesize that the enhanced Wnt/b-catenin signaling in the dura mater alters the production of one or more of these factors.…”

“…The meninges is a neural crest derived tissue that develops in close association with the underlying brain and the overlying frontal and parietal bones (Jiang et al, 2002). Of note, meningeal defects have previously been shown to adversely affect bone formation during embryonic development (Ito et al, 2003;Vivatbutsiri et al, 2008). Conversely, an intact dura mater has been shown to aid in osteogenic repair following calvarial defects (Levi et al, 2011).…”

Craniofacial features resembling frontonasal dysplasia with a tubulonodular interhemispheric lipoma in the adult 3H1 tuft mouse

“…The lipoma probably presented a mechanical barrier restricting normal suture formation joining the cranial bones. It has been shown that defective meningeal development can impede calvarial bone osteogenesis (Opperman et al, 1995; Vivatbutsiri et al, 2008). Thus the abnormal sutural arrangement could be due, in part, to defective meningeal formation altering the expression of relevant osteogenic promoting genes such as Sox9 for the posterior frontal suture (Sahar et al, 2005) or Msx1 for the interfrontal suture (Satokata and Maas, 1994).…”

The transcription factor Foxc1 is necessary for Ihh–Gli2-regulated endochondral ossification

“…Foxc1 ch (congenital hydrocephalus, ch) heterozygous mice were purchased from the Jackson Laboratory (Bar Harbour, ME, USA) and maintained on a standard 12:12-h light/dark cycle. Homozygous Foxc1 ch/ch mice were obtained by mating heterozygous Foxc1 ch/ þ mice 65 . To determine mouse genotypes, genomic DNA was amplified using a Foxc1-specific primer pair (sense primer: 5 0 -TATGAGCGTGTACTCGCACCCT-3 0 ; antisense primer: 5 0 -CGTACCGTTCT CCGTCTTGATGTC-3 0 ) and PCR products were then digested with Cac8I (ref.…”