Independent regulation of Sox3 and Lmx1b by FGF and BMP signaling influences the neurogenic and non-neurogenic domains in the chick otic placode

Abstract

The development of neural tissue starts with the activation of early neural genes such as the SoxB1 transcription factors, which are expressed in response to signaling molecules. Neural progenitors in the inner ear are only generated in the anterior placodal domain, but the mechanisms that determine when and how otic neural fate is acquired are still unknown. Here, we show that Sox3 expression becomes restricted to the anterior territory of the chick otic field and that misexpression of Sox3 induces Sox2 and Delta1 in the non-neurogenic otic territory. This suggests that Sox3 plays a central role in the establishment of an otic neural fate. Furthermore, Sox3 down-regulates the expression of Lmx1b, a marker of the posterior non-neurogenic otic epithelium. The expression of Sox3 is maintained by the positive action of FGF8 derived from the otic ectoderm. On the contrary, BMP signaling does not have a major influence on neural commitment but instead regulates Lmx1b expression in the otic placode. Together, the data support the notion that Sox3 is critical for the development of the neural elements of the inner ear, and they highlight the importance of localized signaling from the ectoderm in establishing the neurogenic vs. non-neurogenic anteroposterior asymmetry that characterizes the early otic placode.