Mapping of Wnt, frizzled, and Wnt inhibitor gene expression domains in the avian otic primordium

Abstract

Wnt signaling activates at least three different pathways involved in development and disease. Interactions of secreted ligands and inhibitors with cell-surface receptors result in the activation or regulation of particular downstream intracellular cascades. During the developmental stages of otic vesicle closure and beginning morphogenesis, the forming inner ear transcribes a plethora of Wnt-related genes. We report expression of 23 genes out of 25 tested in situ hybridization probes on tissue serial sections. Sensory primordia and Frizzled gene expression share domains, with Fzd1 being a continuous marker. Prospective nonsensory domains express Wnts, whose transcripts mainly flank prosensory regions. Finally, Wnt inhibitor domains are superimposed over both prosensory and nonsensory otic regions. Three Wnt antagonists, Dkk1, SFRP2, and Frzb are prominent. Their gene expression patterns partly overlap and change over time, which adds to the diversity of molecular micro-environments. Strikingly, prosensory domains express Wnts transiently. This includes (1) the prosensory otic region of high proliferation, neuroblast delamination, and programmed cell death at stage 20/21 (Wnt3,, and (2) sensory primordia at stage 25 (Wnt7a, Wnt9a). In summary, robust Wnt-related gene expression shows both spatial and temporal tuning during inner ear development as the otic vesicle initiates morphogenesis and prosensory cell fate determination.

Gene-expression analysis of hair cell regeneration in the zebrafish lateral line

“…Our analyses focused on pathways involved in hair cell development as they might be reused during regeneration (15,23,43,78,79). For example, Wnt/β-catenin signaling is crucial for the development of many organs across the animal kingdom (80).…”

Divergent roles for Wnt/β-catenin signaling in epithelial maintenance and breakdown during semicircular canal formation

“…How Wnt/β-catenin functionally integrates with other signaling pathways to sculpt the SSCs and their corresponding sensory patches is currently unknown. Interrogating the spatial and temporal requirements of Wnt/β-catenin signaling is confounded by the multitude of Wnt ligands expressed in and around the inner ear and the redundant manner in which they often function (Sienknecht and Fekete, 2008;Sienknecht and Fekete, 2009). To circumvent these concerns, we developed a conditional gene targeting strategy that uses a tamoxifen-inducible form of Cre recombinase expressed under the transcriptional control of a Wnt-responsive promoter (Top-creER…”

Serial Analysis of Gene Expression in the Chicken Otocyst

“…Of the 172 genes that we identified in this group, several were previously known in inner ear development and include BMP7, FGF10, FGF19, FRZB, TGFß2, NETRIN1, SLIT1, WNT3, and WNT5A (Abraira et al 2008;Alsina et al 2004;Battisti and Fekete 2008;Hollyday et al 1995;Liu et al 2008;Oh et al 1996;Okano et al 2005;Sanchez-Calderon et al 2007;Sienknecht and Fekete 2009). Transcripts encoding the secreted signaling protein midkine (MDK) were by far the most abundantly expressed mRNA that we detected.…”

“…Probably the most interesting group of genes that we identified encodes receptors for signaling proteins because they might reveal information about the developmental processes happening in the otocyst. These include genes that encode receptors for ligands that are already known for playing roles in otic development such as FGFR1, FZD1, FZD2, FZD3, FZD4, FZD7, NGFR, and NOTCH1, which have previously been shown to be expressed in the vertebrate otocyst (Adam et al 1998;Pirvola et al 2002;Sienknecht and Fekete 2009;Stevens et al 2003;von Bartheld et al 1991;Wright and Mansour 2003). BMPR1, BMPR2, LGFR1, SMO1, PTCH1, DISP1, and TGFBR2 are genes that were presumed to be expressed in the otocyst because their ligands, such as BMPs and other TGFß family members, IGF, as well as hedgehog signaling proteins, have been shown to be expressed and active during inner ear development (Bok et al 2005;Frenz et al 1991Frenz et al , 1992Liu et al 2002;Oh et al 1996;Riccomagno et al 2002;Yamashita and Oesterle 1995).…”