Role of Bone morphogenetic protein 4 in zebrafish semicircular canal development

Abstract

Bone morphogenetic proteins (BMPs) are known to play roles in inner ear development of higher vertebrates. In zebrafish, there are several reports showing that members of the BMP family are expressed in the otic vesicle. We have isolated a novel zebrafish mutant gallery, which affects the development of the semicircular canal. Gallery merely forms the lateral and the immature anterior protrusion, and does not form posterior and ventral protrusions. We found that the expression of bmp2b and bmp4, both expressed in the normal optic vesicle at the protrusion stage, are extremely upregulated in the otic vesicle of gallery. To elucidate the role of BMPs in the development of the inner ear of zebrafish, we have applied excess BMP to the wild-type otic vesicle. The formation of protrusions was severely affected, and in some cases, they were completely lost in BMP4-treated embryos. Furthermore, the protrusions in gallery treated with Noggin were partially rescued. These data indicate that BMP4 plays an important role in the development of protrusions to form semicircular canals.

BMP Signaling Is Necessary for Patterning the Sensory and Nonsensory Regions of the Developing Mammalian Cochlea

“…BMP signaling has been suggested to play a role in the formation of the cristae and semicircular canals (Chang et al, 2002; Blauwkamp et al, 2007; Omata et al, 2007; Chang et al, 2008; Hammond et al, 2009; Vervoort et al, 2010). To determine the effects of Alk3 and Alk6 deletion on inner ear morphogenesis, we used paint-filling to analyze the morphology of Alk3 -CKO and Alk3 -CKO; Alk6 +/− mutants at E13.5.…”

Proteomic and functional analysis of NCS-1 binding proteins reveals novel signaling pathways required for inner ear development in zebrafish

“…Dan, Bmp4, and Hyaluronic acid represent secreted molecules that play critical roles in semicircular canal formation [ 13 - 15 , 23 , 43 ] and may require an ncs-1a / arf1 / pi4kβ pathway for secretion. BMPs are expressed in the developing vertebrate inner ear and participate in axial patterning of the otic vesicle and differentiation of the sensory epithelium [ 23 , 44 - 48 ].…”

“…The zebrafish ortholog of the human deafness gene dfna5 , was subsequently shown to be necessary for ugdh expression and proper semicircular canal and jaw development [ 14 ]. Another zebrafish mutant, gallery , displays only a lateral semicircular canal protrusion and an immature anterior protrusion [ 15 ]. Although the gallery gene has not yet been identified, the defects in this mutant are believed to be caused by overexpression of Bmp4 (bone morphogenetic protein 4) in the presumptive cristae.…”

Foxg1 is required for proper separation and formation of sensory cristae during inner ear development

“…Second, genes such as Bone morphogenetic protein‐4 ( Bmp4 ) and Fibroblast growth factor 10 ( Fgf10 ) are primarily expressed in the presumptive cristae, yet engineered deletions of these genes affect cristae as well as canal formation (Pauley et al, 2003; Chang et al, 2008). Third, most existing inner ear mutants of mouse and zebrafish show malformations that involve both cristae and canals, or canals alone (Kiernan et al, 2005; Omata et al, 2007; Hammond et al, 2009). While all of the aforementioned lines of evidence are consistent with the hypothesis of a prospective crista inducing formation of an associated canal, there are a few exceptions in which mouse mutants are reported to have a normal canal in the absence of its crista/ampulla.…”