Abstract
The Eph family receptor-interacting (ephrin) ligands and erythropoietin-producing hepatocellular carcinoma (Eph) receptors constitute the largest known family of receptor tyrosine kinases. Ephrin ligands and their receptors form an important cell communication system with widespread roles in normal physiology and disease pathogenesis. In order to investigate potential roles of the ephrin-Eph system during palatogenesis and tongue development, we have characterized the cellular mRNA expression of family members EphrinA1-A3, EphA1–A8, and EphrinB2, EphB1, EphB4 during murine embryogenesis between embryonic day 13.5–16.5 using radioactive in situ hybridization. With the exception of EphA6 and ephrinA3, all genes were regionally expressed during the process of palatogenesis, with restricted and often overlapping domains. Transcripts were identified in the palate epithelium, localized at the tip of the palatal shelves, in the mesenchyme and also confined to the medial epithelium seam. Numerous Eph transcripts were also identified during tongue development. In particular, EphA1 and EphA2 demonstrated a highly restricted and specific expression in the tongue epithelium at all stages examined, whereas EphA3 was strongly expressed in the lateral tongue mesenchyme. These results suggest regulatory roles for ephrin-EphA signaling in development of the murine palate and tongue.
Highlights
The formation of a palate separating the oral and nasal cavities is a developmental process characteristic of higher vertebrates and requires complex and highly coordinated molecular interactions
EphrinA1 transcripts were identified in the palate epithelium from E13.5 to E16.5 (Figures 2A–D), at the tip of the palatal shelf at E13.5 (Figure 2A, highlighted) with strong expression throughout the oral surface of the palatal shelf epithelium at E14.5 (Figure 2B, highlighted)
EphrinA2 showed no specific epithelial expression in the palate at E13.5, transcripts were present in the mesenchyme (Figure 2E, highlighted); by E14.5 distinct transcriptional activity was observed in the MES (Figure 2F, highlighted)
Summary
The formation of a palate separating the oral and nasal cavities is a developmental process characteristic of higher vertebrates and requires complex and highly coordinated molecular interactions (reviewed in Ferguson, 1988; Cobourne, 2004; Dudas et al, 2007; Gritli-Linde, 2007). The primary palate is a derivative of the frontonasal process, whilst the secondary palate forms from the paired palatal shelves of the maxillary process, themselves a derivative of the first pharyngeal arch. The palate is formed by elevation and fusion of the maxillary palatal shelves, with each other posteriorly, with the primary palate anteriorly and the nasal septum superiorly (reviewed in Dudas et al, 2007). By E14.5 the shelves have elevated above the tongue and grown to meet their counterpart at the midline, where the layers of epithelium adhere and fuse with each other to achieve continuity in the roof of the oral cavity (Figures 1A–L)
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