br Methods br Results Top panels of the Fig show

Methods
Results Top panels of the Fig. 1 show the conventional representation of the predicted values of TL,CO according to ERS’93 and GLI′17 as a function of age and keeping the height constant (160 cm, panel A and 190 cm, panel B). This figure shows that the GLI-‘17 predicted values of TL,CO are systematically lower than those of ERS-’93, except for short males at advanced age.
Conclusion
Funding
Introduction Primary cilia are ubiquitous microtubule-based cellular projections that are specialized for transducing extracellular signaling cues. Functional disruptions to the primary cilia are associated with a spectrum of complex human genetic disorders known as ciliopathies (Badano et al., 2006, Baker and Beales, 2009, D'Angelo and Franco, 2010, Goetz and Anderson, 2010). Craniofacial dysmorphologies are common characteristics of the ciliopathic disease spectrum. Approximately 30% of known human ciliopathies are primarily characterized by their craniofacial defects (Chang et al., 2015, Tobin et al., 2008, Zaghloul and Brugmann, 2011). Oral malformations, including those affecting the development of the tongue, are among the most common phenotypes present in craniofacial ciliopathies. Ciliopathic conditions such as Oral-facial-digital syndrome, Meckel-Gruber syndrome, and Joubert syndrome frequently present with glossal abnormalities including: an abnormally small tongue (microglossia), bifid or cleft tongue, anterior marginal hamartomas or cysts of the tongue, and tongue tumors (Chang et al., 2015, Gai et al., 2012, Moran-Barroso et al., 1998, Parisi, 2009). Although glossal abnormalities are common occurrences among ciliopathies and have a significant impact on the feeding and speech of patients, the underlying developmental mechanisms that affect glossal development in ciliopathies have not been explored. The tongue and several other facial structures affected in ciliopathies are derivatives of, or have a substantial contribution from neural crest Clonidine HCl (NCCs). NCCs are a migratory, multipotent cell population that migrate from the dorsal neural tube to populate the facial prominences, including the pharyngeal arches from which the tongue is derived (Noden et al., 1999). Development of the tongue begins with the emergence of a swelling composed of NCCs on the floor mandible called the median lingual swelling (Parada et al., 2012, Salles et al., 2008). During this stage, the vast majority of the tongue anlage is composed of NCC-derived mesenchymal cells (Han et al., 2012, Parada and Chai, 2015, Parada et al., 2012). Subsequently, bilateral elevations called the lateral lingual swellings emerge on either side of the medial lingual swelling. Simultaneously, mesoderm-derived mesenchymal cells migrate from the occipital somites into the lingual swellings to give rise to the intrinsic glossal musculature (Han et al., 2012, Noden and Francis-West, 2006). It is believed that reciprocal interactions between NCCs and myogenic precursor cells play an essential role in regulating tongue development, whereby NCCs initiate and direct the proliferation and differentiation of myoblasts into muscle (Han et al., 2012, Hosokawa et al., 2010). Several signaling pathways have been implicated in glossal development. Non-canonical and canonical Transforming Growth Factor-β (TGF-β) signaling in NCCs have been reported to control the proliferation and organization of glossal muscles, after the formation of the tongue bud (Hosokawa et al., 2010, Parada and Chai, 2015). Hand2, via the negative regulation of Dlx5 and Dlx6 expression in the distal arch ectomesenchyme, patterns the distal portion of the mandible and is essential in the initiation of the tongue mesenchyme morphogenesis (Barron et al., 2011). Finally, canonical Fox mediated Hh signaling in NCCs is essential for normal patterning and growth of the face, including the mandible and the tongue (Jeong et al., 2004). Primary cilia are important for the transduction of these, and several other signaling pathways during development.