Bones, Glands, Ears and More: The Multiple Roles of FGF10 in Craniofacial Development

Abstract

Members of the fibroblast growth factor (FGF) family have myriad functions during development of both non-vertebrate and vertebrate organisms. One of these family members, FGF10, is largely expressed in mesenchymal tissues and is essential for postnatal life because of its critical role in development of the craniofacial complex, as well as in lung branching. Here, we review the function of FGF10 in morphogenesis of craniofacial organs. Genetic mouse models have demonstrated that the dysregulation or absence of FGF10 function affects the process of palate closure, and FGF10 is also required for development of salivary and lacrimal glands, the inner ear, eye lids, tongue taste papillae, teeth, and skull bones. Importantly, mutations within the FGF10 locus have been described in connection with craniofacial malformations in humans. A detailed understanding of craniofacial defects caused by dysregulation of FGF10 and the precise mechanisms that underlie them offers new opportunities for development of medical treatments for patients with birth defects and for regenerative approaches for cancer patients with damaged gland tissues.

Fgf10/Fgfr2b Signaling in Mammary Gland Development, Homeostasis, and Cancer

“…Fgf10 plays therefore important roles both before the induction of the AER (which was thought to be the earliest event in limb formation) as well as before mammary placode induction. It is not clear if this dual function played by Fgf10 prior and after organ induction is also conserved for other branched structures either endoderm-derived (lung, pancreas, cecum) or ectoderm-derived (teeth, tongue, palatal shelves as well as salivary and lacrimal glands for example) [For a comprehensive review on the role of Fgf10 in cranio-facial development see (Prochazkova et al, 2018 )]. Interestingly, in both endoderm [especially the lung, see (Jones et al, 2018 )] and ectoderm-derived organs (particularly for the cleft palate), a common feature appears to be the role of Fgf10 signaling in modulating cell adhesion.…”

First‐Trimester Nonvisualization of the Parotid Gland and Aneuploidy in Fetuses With Increased Nuchal Translucency

“…19 Fibroblast growth factor 10 signaling plays important roles in the development of several craniofacial structures, including the salivary glands, lacrimal glands, palate, eyelids, inner ear, tongue, teeth, and skull. [29][30][31] Mutations in FGF10 have been found to cause numerous developmental defects and abnormalities in humans, such as malformations and agenesis of involved organs. 31,32 In mouse models, FGF10-null embryos show aplasia of the salivary glands, with their development arrested at the bud stage.…”

“…[29][30][31] Mutations in FGF10 have been found to cause numerous developmental defects and abnormalities in humans, such as malformations and agenesis of involved organs. 31,32 In mouse models, FGF10-null embryos show aplasia of the salivary glands, with their development arrested at the bud stage. Other abnormalities caused by disruption of FGF10 expression in mice include anomalies of the inner ear, teeth, limbs, midface, thyroid, pituitary gland, thymus, stomach, pancreas, and genitourinary system.…”

Extracellular Matrix Composition and Remodeling: Current Perspectives on Secondary Palate Formation, Cleft Lip/Palate, and Palatal Reconstruction

“…The actions of numerous morphogens in palatogenesis have been extensively studied, mainly secreted factors such as HH (Cobourne and Green, 2012;Dworkin et al, 2016;Xavier et al, 2016;, FGF (Jiang et al, 2006;Nie et al, 2006;Snyder-Warwick and Perlyn, 2012;Stanier and Pauws, 2012;Prochazkova et al, 2018;Weng et al, 2018), TGF-β (Nawshad et al, 2004;Iwata et al, 2011;Nakajima et al, 2018), BMP (Nie et al, 2006;Parada and Chai, 2012;Graf et al, 2016), and Wnt/β-catenin family proteins (He and Chen, 2012), which are responsible for guiding all steps of palate formation by reciprocal signaling between the embryonic oral epithelium and palatal mesenchyme, as well as transcription factor regulation (Greene and Pisano, 2010;Levi et al, 2011;Bush and Jiang, 2012;Li et al, 2017). Also, other morphogens and growth factors have emerged in palatogenesis, such as connective tissue growth factor (Tarr et al, 2018) and retinoic acid (Okano et al, 2014;Mammadova et al, 2016).…”