Genetic interactions underlying otic placode induction and formation

Abstract

The formation of the otic placode is a complex process requiring multiple inductive signals. In zebrafish, fgf3 and fgf8, dlx3b and dlx4b, and foxi1 have been identified as the earliest-acting genes in this process. fgf3 and fgf8 are required as inductive signals, whereas dlx3b, dlx4b, and foxi1 appear to act directly within otic primordia. We have investigated potential interactions among these genes. Depletion of either dlx3b and dlx4b or foxi1 leads to a delay of pax2a expression in the otic primordia and reduction of the otic vesicle. Depletion of both foxi1 and dlx3b results in a complete ablation of otic placode formation. A strong synergistic interaction is also observed among foxi1, fgf3, and fgf8, and a weaker interaction among dlx3b, fgf3, and fgf8. Misexpression of foxi1 can induce expression of pax8, an early marker for the otic primordia, in embryos treated with an inhibitor of fibroblast growth factor (FGF) signaling. Conversely, morpholino knockdown of foxi1 blocks ectopic pax8 expression and otic vesicle formation induced by misexpression of fgf3 and/or fgf8. The observed genetic interactions suggest a model in which foxi1 and dlx3b/dlx4b act in independent pathways together with distinct phases of FGF signaling to promote otic placode induction and development. Developmental Dynamics 230:419 -433, 2004.

The first steps towards hearing: mechanisms of otic placode induction

“…Unlike foxi1 mutants, morpholino knockdowns of dlx3b and dlx4b still expressed pax8. Taken together, these results suggest a model where foxi1 would be involved in the induction of pax8 while dlx3b and dlx4b would act later in the induction of pax2 (Hans et al, 2004, Solomon et al, 2004. Loss of either pax8 or pax2 in fish as well as in mouse did not affect the induction of the otic placode (Torres et al, 1996, Mansouri et al, 1998, Riley et al, 1999, Whitfield et al, 2002, Hans et al, 2004.…”

“…No double mutants for Pax2 and Pax8 have been described in mouse. The growing body of work on the interactions between the foxi1, dlx3b, dlx4b, pax2 and pax8 in zebrafish has been summarized by Solomon and colleagues (Solomon et al, 2004), Riley and Phillips (Riley and Phillips, 2003) and Hans and colleagues (Hans et al, 2004). However, further experiments need to be conducted to determine whether this network of transcription factor interactions also applies to other species.…”

“…It is important to note, however, that some aspects of otic placode induction are FGF-independent. For example, in zebrafish induction of foxi1, dlx4 and sox9b are unaffected in mutants lacking both fgf3 and fgf8 (Solomon et al, 2004). Indeed, foxi1 has been proposed to act as a competence factor in fish, allowing ectoderm to respond to FGF signaling, but not itself responding to FGFs (Hans et al, 2004, Hans et al, 2007, although Phillips and colleagues have shown that fgf8 mis-expression induced ectopic domains of expression of foxi1 (Phillips et al, 2004).…”

“…Indeed, foxi1 has been proposed to act as a competence factor in fish, allowing ectoderm to respond to FGF signaling, but not itself responding to FGFs (Hans et al, 2004, Hans et al, 2007, although Phillips and colleagues have shown that fgf8 mis-expression induced ectopic domains of expression of foxi1 (Phillips et al, 2004). In addition, zebrafish dlx3b has also been reported to be FGF-independent in some studies but not others (Leger and Brand, 2002, Maroon et al, 2002, Liu et al, 2003, Solomon et al, 2004. The factors responsible for the expression of foxi1, dlx3b, dlx4b and sox9a are not known, although it has been recently suggested that BMP signaling might be a candidate for foxi1 and dlx3b induction (Hans et al, 2007).…”

The preplacodal region: an ectodermal domain with multipotential progenitors that contribute to sense organs and cranial sensory ganglia

“…In contrast, loss of both genes completely abolishes the formation of otic structures (Solomon, et al, 2004;Hans, et al, 2007). Experiments in Xenopus demonstrate an even earlier role for FoxiI; loss of FoxiIa function leads to an expansion of the neural plate at gastrula stages, while its overexpression suppresses neural development while simultaneously promoting epidermal character (MatsuoTakasaki, et al, 2005).…”