All cranial sensory organs and sensory neurons of vertebrates develop from cranial
placodes. In chick, amphibians and zebrafish, all placodes originate from a common
precursor domain, the pre-placodal region (PPR), marked by the expression of Six1/4
and Eya1/2. However, the PPR has never been described in mammals and the mechanism
involved in the formation of PPR is poorly defined. Here, we report the expression
of Six1 in the horseshoe-shaped mouse ectoderm surrounding the anterior neural plate
in a pattern broadly similar to that of non-mammalian vertebrates. To elucidate the
identity of Six1-positive mouse ectoderm, we searched for enhancers responsible for
Six1 expression by in vivo enhancer assays. One conserved non-coding sequence, Six1-14,
showed specific enhancer activity in the rostral PPR of chick and Xenopus and in the
mouse ectoderm. These results strongly suggest the presence of PPR in mouse and that
it is conserved in vertebrates. Moreover, we show the importance of the homeodomain
protein-binding sites of Six1-14, the Six1 rostral PPR enhancer, for enhancer activity,
and that Dlx5, Msx1 and Pax7 are candidate binding factors that regulate the level
and area of Six1 expression, and thereby the location of the PPR. Our findings provide
critical information and tools to elucidate the molecular mechanism of early sensory
development and have implications for the development of sensory precursor/stem cells.
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