Gata3 is required for early morphogenesis and Fgf10 expression during otic development

Abstract

Inner ear develops from an induced surface ectoderm placode that invaginates and closes to form the otic vesicle, which then undergoes a complex morphogenetic process to form the membranous labyrinth. Inner ear morphogenesis is severely affected in Gata3 deficient mouse embryos, but the onset and basis of the phenotype has not been known. We show here that Gata3 deficiency leads to severe and unique abnormalities during otic placode invagination. The invagination problems are accompanied often by the formation of a morphological boundary between the dorsal and ventral otic cup and by the precocious appearance of dorsal endolymphatic characteristics. In addition, the endolymphatic domain often detaches from the rest of the otic epithelium during epithelial closure. The expression of several cell adhesion mediating genes is altered in Gata3 deficient ears suggesting that Gata3 controls adhesion and morphogenetic movements in early otic epithelium. Inactivation of Gata3 leads also to a loss of Fgf10 expression in otic epithelium and auditory ganglion demonstrating that Gata3 is an important regulator of Fgf-signalling during otic development.

Dynamic Expression of Lgr5, a Wnt Target Gene, in the Developing and Mature Mouse Cochlea

“…Previously, Wnt signaling was shown to mediate otic versus epidermal fate decisions during the formation of otic placode (Lillevali et al 2006;Ohyama et al 2006). In the developing chicken inner ear, Fekete (2008, 2009) Lgr5 is an orphan G protein-coupled receptor with a large leucine-rich domain, but lacks a clearly defined function (Hsu et al 1998).…”

“…Multiple genes are expressed within the cochlear prosensory domain, including Jagged1, Islet1, Lunatic fringe, Prox1, Sox2, and Fgf20 (Bermingham-McDonogh et al 2006;Dabdoub et al 2008;Hayashi et al 2008;Kiernan et al 2005;Morrison et al 1999;Morsli et al 1998;Radde-Gallwitz et al 2004). Wnt/ß-catenin signaling is involved in the specification of otic cell identity, dorsal patterning of the otocyst, as well as eventual formation of the vestibular organs (Hollyday et al 1995;Jasoni et al 1999;Lillevali et al 2006;Ohyama et al 2006;Riccomagno et al 2005). However, few studies have examined the role of this signaling pathway in the developing cochlea in the late embryonic age.…”

Gata2 is required for the development of inner ear semicircular ducts and the surrounding perilymphatic space

“…6H,L and data not shown). Similarly, no change was observed in the expression of Gata3 at E12.5 or E14.5 (data not shown), which is at these stages expressed in restricted areas of vestibular nonsensory epithelium and periotic mesenchyme in addition to the sensory areas (Lillevä li et al, 2004(Lillevä li et al, , 2006. In summary, these observations suggested that the inactivation of Gata2 did not cause any major defects in cell differentiation and fate determination of the otic epithelium.…”

“…Gata2 is expressed in the developing inner ear of mouse and chicken together with another family member, Gata3 (Lillevä li et al, 2004(Lillevä li et al, , 2006. The expression of Gata2 starts in mouse otic vesicle at E9.5, while Gata3 expression is activated already in the otic placode (Lillevä li et al, 2004(Lillevä li et al, , 2006.…”

“…The expression of Gata2 starts in mouse otic vesicle at E9.5, while Gata3 expression is activated already in the otic placode (Lillevä li et al, 2004(Lillevä li et al, , 2006. The expression of these two family members is highly overlapping in the early otic vesicle, but becomes more diverse at later developmental stages.…”