The aim of this application is to study the role of Dlx genes in neurogenic cranial placode induction. The neurogenic cranial placodes are discrete regions of thickened ectoderm that are visible in early development at the anterior border of the neural plate. These placodes will give rise to the majority of sensory and neural tissue in the olfactory system, the inner ear, and the cranial sensory ganglia. The molecular mechanisms underlying the induction of these placodes are not known. Numerous observations suggest that the ectoderm fated to produce the neurogenic cranial placodes acquires general placode competence prior to specific placode induction, although there is no direct evidence that such a state exists or is necessary. A number of genes, including Dlx5 and Dlx6, are expressed in a pattern marking the pre-placodal ectoderm, however their roles in placode induction have not been carefully examined. We hypothesize that the neurogenic cranial placodes will not be properly induced unless the ectoderm at the anterior neural plate border giving rise to these placodes acquires general placode competence. We further hypothesize that Dlx5 and/or Dlx6 are necessary for the generation of this state of general placode competence, thus being necessary for the induction of all neurogenic cranial placodes.
SPECIFIC AIM 1 : To test the necessity of Dlx5 and/or Dlx6 for neurogenic cranial placode induction, we will use dominant- negative Dlx5 and Dlx6 expression in the pre-placodal ectoderm of chick embryos to locally inhibit endogenous Dlx5 and Dlx6 activity. Effects on subsequent placode induction will determine the necessity of Dlx5 and/or Dlx6 for this process and clarify whether or not a state of general placode competence precedes neurogenic placode induction.
SPECIFIC AIM 2 : To test the sufficiency of Dlx5 and Dlx6 to induce a state of placode competence in uncommitted ectoderm, we will test the ability of uncommitted epiblast tissue transfected with Dlx5 and Dlx6 to respond in vitro to specific placode-inducing tissues. The expression of specific placodal markers in epiblast following co-culture will establish the sufficiency of Dlx5 and/or Dlx6 to induce general placode competence in ectoderm uncommitted to any specific tissue fate.
| Brown, Stephen T; Wang, Juemei; Groves, Andrew K (2005) Dlx gene expression during chick inner ear development. J Comp Neurol 483:48-65 |
| Brown, Stephen T; Martin, Kareen; Groves, Andrew K (2003) Molecular basis of inner ear induction. Curr Top Dev Biol 57:115-49 |
