Hearing impairment is a growing public health concern. In the United States, 1 in 1000 newborns has hereditary hearing disabilities and 50% of the American population suffer hearing problem by the age of 65. Many forms of hereditary hearing loss affect early events in the development of the inner ear. Understanding the molecular pathways involved in early ear development may therefore advance our understanding of hereditary deafness. All craniofacial sensory organs are derived from an embryonic region called the pre-placodal region (PPR). The PPR is marked by the expression of unique set of genes like Dlx5, ERNI, Six1/4, Foxi3 and Eya 1/2. We have shown that Foxi3 is one of the earliest genes expressed in this region. Deletion of Foxi3 in mouse results in complete morphological loss of inner ear and its precursor, the otic placode. The role of FGF in ear development is well established. Our lab showed that only PPR ectoderm was able to induce otic placode markers in the presence of FGF whereas ectoderm far lateral to the PPR could not. This experiment suggests that genes expressed in the PPR might be responsible for providing FGF responsiveness. Several Forkhead genes have been proposed to act as competence factors in the development of the liver, pancreas and lens. It is therefore possible that Foxi3 acts as competence factor in ear development. The main objective of our study is to understand the role of Foxi3 in otic placode induction using chick and mouse as model systems.
Our specific aims will be as followed: 1) Is Foxi3 necessary and sufficient to induce PPR genes? 2) Is Foxi3 necessary to induce the otic placode? 3) Does Foxi3 gene provide competence to respond to FGF signaling?
All sensory organs, such as the ear, nose and lens of eye are produced by a common region of skin next to the embryonic brain. This project will focus on understanding the role of Foxi3 gene in ear development and identify genes that are regulated by Foxi3. The long term goal is to use this information for understanding the molecular mechanisms behind ear development.
|Khatri, Safia B; Edlund, Renée K; Groves, Andrew K (2014) Foxi3 is necessary for the induction of the chick otic placode in response to FGF signaling. Dev Biol 391:158-69|
|Khatri, Safia B; Groves, Andrew K (2013) Expression of the Foxi2 and Foxi3 transcription factors during development of chicken sensory placodes and pharyngeal arches. Gene Expr Patterns 13:38-42|