IdGene Regulation and Function in the Prosensory Domains of the Chicken Inner Ear: A Link between Bmp Signaling andAtoh1

Autor: Fernando Giraldez, Joana Neves, Andrés Kamaid
Rok vydání: 2010
Předmět:
Zdroj: The Journal of Neuroscience. 30:11426-11434
ISSN: 1529-2401
0270-6474
DOI: 10.1523/jneurosci.2570-10.2010
Popis: Bone morphogenetic proteins (Bmps) regulate the expression of the proneural geneAtoh1and the generation of hair cells in the developing inner ear. The present work explored the role ofInhibitor of Differentiationgenes (Id1-3) in this process. The results show thatIdgenes are expressed in the prosensory domains of the otic vesicle, along withBmp4andBmp7. Those domains exhibit high levels of the phosphorylated form of Bmp-responding R-Smads (P-Smad1,5,8), and of Bmp-dependent Smad transcriptional activity as shown by the BRE-tk-EGFP reporter. Increased Bmp signaling induces the expression ofId1-3along with the inhibition ofAtoh1. Conversely, the Bmp antagonist Noggin or the Bmp-receptor inhibitor Dorsomorphin elicit opposite effects, indicating that Bmp signaling is necessary forIdexpression andAtoh1regulation in the otocyst. The forced expression ofId3is sufficient to reduceAtoh1expression and to prevent the expression of hair cell differentiation markers. Together, these results suggest thatIdsare part of the machinery that mediates the regulation of hair cell differentiation exerted by Bmps. In agreement with that, during hair cell differentiationBmp4expression, P-Smad1,5,8 levels andIdexpression are downregulated from hair cells. However,Idsare also downregulated from the supporting cells which contrarily to hair cells exhibit high levels ofBmp4expression, P-Smad1,5,8, and BRE-tk-EGFP activity, suggesting that in these cellsIdsescape from Bmp/Smad signaling. The differential regulation ofIdsin time and space may underlie the multiple functions of Bmp signaling during sensory organ development.
Databáze: OpenAIRE