Using frogs faces to dissect the mechanisms underlying human orofacial defects

Abstract

In this review I discuss how Xenopus laevis is an effective model to dissect the mechanisms underlying orofacial defects. This species has been particularly useful in studying the understudied structures of the developing face including the embryonic mouth and primary palate. The embryonic mouth is the first opening between the foregut and the environment and is critical for adult mouth development. The final step in embryonic mouth formation is the perforation of a thin layer of tissue covering the digestive tube called the buccopharyngeal membrane. When this tissue does not perforate in humans it can pose serious health risks for the fetus and child. The primary palate forms just dorsal to the embryonic mouth and in non-amniotes it functions as the roof of the adult mouth. Defects in the primary palate result in a median oral cleft that appears similar across the vertebrates. In humans, these median clefts are often severe and surgically difficult to repair. Xenopus has several qualities that make it advantageous for craniofacial research. The free living embryo has an easily accessible face and we have also developed several new tools to analyze the development of the region. Further, Xenopus is readily amenable to chemical screens allowing us to uncover novel gene-environment interactions during orofacial development, as well as to define underlying mechanisms governing such interactions. In conclusion, we are utilizing Xenopus in new and innovative ways to contribute to craniofacial research.

E-cigarette aerosol exposure can cause craniofacial defects in Xenopus laevis embryos and mammalian neural crest cells

“…This species is amenable to screening studies since they are free living, large in size, develop rapidly, and can be obtained in great numbers [ 44 ] add more refs. Further, Xenopus is emerging as an effective model to understand craniofacial development [ 45 – 52 ]. The orofacial region is readily visible, unlike other model vertebrates where head flexure obscures easy viewing of the face, making evaluation of craniofacial development faster and easier [ 45 ].…”

“…Further, Xenopus is emerging as an effective model to understand craniofacial development [ 45 – 52 ]. The orofacial region is readily visible, unlike other model vertebrates where head flexure obscures easy viewing of the face, making evaluation of craniofacial development faster and easier [ 45 ]. Further, we have also developed a quantitative method to assess X .…”

Modeling Human Craniofacial Disorders in Xenopus

“…Animal models have informed much of the current understanding of OFCs, despite the obvious and stark differences in facial morphology of the vertebrates, because of the conserved underlying mechanisms. In that respect, Xenopus is an extremely useful experimental model as the orofacial region is readily visible and can be easily dissected and transplanted [45]. …”

Expanding the genetic toolkit in Xenopus: Approaches and opportunities for human disease modeling

“…Xenopus animals and oocytes are used extensively to understand normal organ function and disease in humans (Labonne and Zorn, 2015), including cardiac congenital heart disorders and heterotaxy (Boskovski et al, 2013; Duncan and Khokha, 2016; Fakhro et al, 2011; Kaltenbrun et al, 2011; Langdon et al, 2012; 2007), gastrointestinal and pancreatic diseases (Kofent and Spagnoli, 2016; Pearl et al, 2009; 2011; Salanga and Horb, 2015; Womble et al, 2016), endocrine functions and disorders (Buchholz, 2015), kidney disease (Lienkamp, 2016), lung development (Rankin et al, 2011; 2015; Wallmeier et al, 2014), cancer (Chernet and Levin, 2013; Cross and Powers, 2009; Hardwick and Philpott, 2015; Haynes-Gilmore et al, 2014; Van Nieuwenhuysen et al, 2015; Wylie et al, 2015), ciliopathies (Kim et al, 2010; Klos Dehring et al, 2013; Ma et al, 2014), orofacial defects (Dickinson, 2016), and neurodevelopmental disorders (Erdogan et al, 2016; Pratt and Khakhalin, 2013). Looking forward, Xenopus is poised to take advantage of the new developments in genomics and genome engineering to better understand the molecular mechanisms underlying human disease (Harland and Grainger, 2011; Labonne and Zorn, 2015).…”