Morphogenesis of the inner ear epithelium requires coordinated deployment of several signaling pathways, and disruptions cause abnormalities of hearing and/or balance. The FGFR2b ligands FGF3 and FGF10 are expressed throughout otic development and are required individually for normal morphogenesis, but their prior and redundant roles in otic placode induction complicates investigation of subsequent combinatorial functions in morphogenesis. To interrogate these roles and identify new effectors of FGF3 and FGF10 signaling at the earliest stages of otic morphogenesis, we used conditional gene ablation after otic placode induction, and temporal inhibition of signaling with a secreted, dominant-negative FGFR2b ectodomain. We show that both ligands are required continuously after otocyst formation for maintenance of otic neuroblasts and for patterning and proliferation of the epithelium, leading to normal morphogenesis of both the cochlear and vestibular domains. Furthermore, the first genome-wide identification of proximal targets of FGFR2b signaling in the early otocyst reveals novel candidate genes for inner ear development and function.
Morphogenesis of the inner ear epithelium requires coordinated deployment of several signaling pathways and disruptions cause abnormalities of hearing and/or balance. The FGFR2b ligands, FGF3 and FGF10, are expressed throughout otic development and are required individually for normal morphogenesis, but their prior and redundant roles in otic placode induction complicates investigation of subsequent combinatorial functions in morphogenesis. To interrogate these roles and identify new effectors of FGF3 and FGF10 signaling at the earliest stages of otic morphogenesis, we used conditional gene ablation after otic placode induction and temporal inhibition of signaling with a secreted, dominant-negative FGFR2b ectodomain. We show that both ligands are required continuously after otocyst formation for maintenance of the otic ganglion and patterning and proliferation of the epithelium, leading to normal morphogenesis of both the cochlear and vestibular domains. Furthermore, the first genomewide identification of proximal targets of FGFR2b signaling in the early otocyst reveals novel candidate genes for inner ear development and function.
The aim of this study was to use barium upper gastrointestinal series (UGI) to evaluate the development and natural history of a hiatal hernia. Summary of Background Data: Hiatal hernias are common but the natural history of sliding and paraesophageal type hernias is poorly understood. Methods: We reviewed UGI reports from 1987 to 2017 using a word scanning software program to identify individuals that had a hiatal hernia.Only those with at least 2 UGI studies 5 or more years apart were selected. The studies were then reviewed. Results: There were 89 individuals that met inclusion criteria. Twenty-one people had no hiatal hernia on initial UGI and over a median of 99 months a sliding hiatal hernia (SHH) developed in 16 and a PEH developed in 5 people. A SHH was present on initial UGI in 55 people and at a median of 84 months subsequent UGI showed the SHH was stable in 11 (20%), increased in size in 30 (55%), and changed to a PEH in 14 people (25%). In 13 people a PEH was present on initial UGI and over a median of 97 months it was stable in 5 and increased in size in 8 people (62%). Conclusions: We showed that both SHH and PEH can develop over time and that the majority of both increased in size on follow-up UGI study. Further, 25% of SHH became a PEH over time. Recognizing an increase in size or change in type of a hiatal hernia may be clinically relevant to help understand changing or worsening symptoms in an individual.
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