Fgf8P2A-3×GFP/+: A New Genetic Mouse Model for Specifically Labeling and Sorting Cochlear Inner Hair Cells

Yi Pan1  · Shuting Li2,3 · Shunji He2  · Guangqin Wang2,3 · Chao Li2  · Zhiyong Liu2,4  · Mingliang Xiang1
1 Department of Otolaryngology and Head and Neck Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 
2 Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China 
3 University of Chinese Academy of Sciences, Beijing 100049, China 
4 Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 201210, China

Abstract
The cochlear auditory epithelium contains two types of sound receptors, inner hair cells (IHCs) and outer hair cells (OHCs). Mouse models for labelling juvenile and adult IHCs or OHCs exist; however, labelling for embryonic and perinatal IHCs or OHCs are lacking. Here, we generated a new knock-in Fgf8P2A-3×GFP/+ (Fgf8GFP/+) strain, in which the expression of a series of three GFP fragments is controlled by endogenous Fgf8 cis-regulatory elements. After confirming that GFP expression accurately reflects the expression of Fgf8, we successfully obtained both embryonic and neonatal IHCs with high purity, highlighting the power of Fgf8GFP/+. Furthermore, our fate-mapping analysis revealed, unexpectedly, that IHCs are also derived from inner ear progenitors expressing Insm1, which is currently regarded as an OHC marker. Thus, besides serving as a highly favorable tool for sorting early IHCs, Fgf8GFP/+ will facilitate the isolation of pure early OHCs by excluding IHCs from the entire hair cell pool.

Keywords
Fgf8; Inner Hair Cell; Inner Ear; Cochlea