Potential Role of Sox9 in Patterning Tracheal Cartilage Ring Formation in an Embryonic Mouse Model

Abstract

To identify genes expressed early in the formation of the mouse trachea that control patterning of tracheal cartilaginous rings. Design: The mouse larynx and trachea begin as an outpouching from the ventral foregut endoderm at embryonic day (E) 9. Digoxigenin-labeled RNA probes to putative tracheal patterning genes were generated by in vitro transcription. Embryos ranging in age from E9 to E16 were then subjected to whole-mount in situ hybridization using these labeled RNA probes. The RNA probes were then localized using antidigoxigenin antibodies tagged with a reporter molecule. In this manner, the 3-dimensional spatial and temporal expression of putative tracheal patterning genes was examined.

“Endodermal Wnt signaling is required for tracheal cartilage formation”

“…4 H). Col2a1 is a direct target of Sox9 and it is expressed in developing trachea at E10.5 in a similar distribution to that of Sox9 (Elluru et al, 2009; Elluru and Whitsett, 2004). We utilized Col2a1Cre mice to delete Sox9 in chondrocyte progenitors.…”

“…Mesenchymal cells derived from the splanchnic mesoderm, positioned ventral to the developing tracheal tube express the transcription factor Sox9 as early as E9 (Elluru and Whitsett, 2004; Hines et al, 2013). Sox9 is a key regulator of cartilage and bone development (Akiyama, 2008; Akiyama et al, 2002) and its role in tracheal cartilage has been demonstrated (Arora et al, 2012; Elluru and Whitsett, 2004; Hines et al, 2013; Park et al, 2010; Turcatel et al, 2013). Signaling mechanisms controlling the initial specification of tracheal cartilage progenitors are poorly defined; however, a number of transcription factors, receptors and ligands that influence Sox9 expression in the mesenchyme of the trachea have been identified.…”

Genome‐scale study of transcription factor expression in the branching mouse lung

“…However, Sox9 is also expressed in the proximal mesenchyme, specifically in the precursor and differentiated cartilages of both the trachea and main bronchi (Elluru et al 2004). As Sox9 is a key gene essential for cartilage development (Bi et al 2001), it likely plays a role in airway cartilage ring formation.…”

Developmental Aspects of the Upper Airway: Report from an NHLBI Workshop, March 5-6, 2009

“…Abnormal expression of SHH has been associated with glossoptosis, pyriform aperture stenosis, tracheoesophageal fistula, and/or laryngotracheoesophageal cleft malformations (25). Multiple other cytokines and transcription factors have been implicated in upper airway anomalies (Table 3) (26)(27)(28)(29)(30)(31)(32)(33)(34). It is likely that other mouse models display upper airway abnormalities that have not been identified due to lack of screening by investigators with appropriate knowledge.…”