Difference in apical and basal growth of the frontal bone primordium in Foxc1^ch/ch mice

Abstract

), results in congenital hydrocephalus accompanied by defects in the apical part of the skull vault. We found that during the initiation stage of apical growth of the frontal bone primordium in the Foxc1 ch/ch mouse, the Runx2 expression domain extended only to the basal side and bone sialoprotein (Bsp) and N-cadherin expression domains appeared only in the basal region. Fluorescent dye (DiI) labeling of the frontal primordium by ex-utero surgery confirmed that apical extension of the frontal bone primordium of the mouse was severely retarded, while extension to the basal side underneath the brain was largely unaffected. Consistent with this observation, decreased cell proliferation activity was seen at the apical tip but not the basal tip of the frontal bone primordium as determined by double detection of Runx2 transcripts and BrdU incorporation. Furthermore, expression of the osteogenicrelated genes Bmp4 and-7 was observed only in the basal part of the meninges during the initiation period of primordium growth. These results suggest that a loss of Foxc1 function affects skull bone formation of the apical region and that Bmp expression in the meninges might influence the growth of the calvarial bone primordium.

Foxc1 Expression in Early Osteogenic Differentiation Is Regulated by BMP4‐SMAD Activity

“…Rudimentary frontal and parietal bones are present in the skull vault of Foxc1 ‐null mice. The initial condensations that form bone are present but they are reduced in size and display a reduction in cell proliferation [Rice et al, ; Machida et al, ]. Expression of Foxc1 in the developing skeleton is abundant in similar mesenchymal condensations that eventually form bone [Hiemisch et al, ; Kume et al, ].…”

Developmental biology of the meninges

“…In these mutants, the calvarial bone development was arrested at E13.5, shortly after initiation of osteogenesis in the supraorbital mesenchyme (Rice et al, 2003;Vivatbutsiri et al, 2008). The bone rudiments showed decreased cell proliferation and apical growth (Machida, Okuhara, Harada, & Iseki, 2014;Rice et al, 2003). Importantly, during normal development, Foxc1 is not expressed in the bone rudiments at this age, but instead it is strongly expressed in the underlying meninges (Rice et al, 2003).…”

Transcription factor Foxc1 is involved in anterior part of cranial base formation

“…As facial bones are membranous bones, FOXC1 might be involved in osteoblast differentiation or ossification. It is reported that Foxc1 is briefly expressed in differentiating osteoblasts (Machida et al ). Currently, the information on the cranial base phenotype of the patients is not available, and it is difficult to discuss if the cranial base defects found in the Foxc1 ch/ch are related to human conditions.…”

“…These proteins play roles in a variety of developmental events and diseases, including cell fate determination, proliferation, and differentiation (Carlsson and Mahlapuu 2002;Lehmann et al 2003;Hannenhalli and Kaestner 2009;Benayoun et al 2011). Foxc1 is associated with corneal, meningeal, calvarial, brain vasculature, and cardiovascular development (Kume et al 2001;Seo et al 2006;Vivatbutsiri et al 2008;Machida et al 2014;Prasitsak et al 2015;Fatima et al 2016). Mutations in FOXC1 causes Axenfeld-Rieger syndrome, a congenital disease mainly characterized by abnormal development of the anterior segment of the eye, cardiovascular outflow tract, craniofacial structure, and pituitary gland (Chang et al 2011).…”

“…It has been reported that Foxc1 is also involved in the initial step of intramembranous and endochondral ossification (Rice et al ; Yoshida et al ). Spontaneous loss of Foxc1 function in a mouse ( congenital hydrocephalous ), Foxc1 ch/ch , shows distinct skeletal defects in the skull (Kume et al ; Hong et al ; Rice et al ; Machida et al ); however, previous studies did not show a detailed analysis on the cranial base. In this study, we examined the cranial base formation of Foxc1 ch/ch mice to obtain some insights into Foxc1 function.…”