The histone demethylase KDM4B orchestrates an early step in the development of the inner ear, Uribe et al. show.
The inner ear starts out as a slab of ectoderm, the otic placode, that buckles and bends into a spherical structure known as the otic vesicle. At the same time the otic placode is forming, early embryos produce KDM4B, which switches on genes by removing the H3K9me3 epigenetic mark.
Uribe et al. found that KDM4B was expressed in the otic placode of early chick embryos, coincident with a decline in H3K9me3 levels in the placode. Otic vesicles in KDM4B-deficient embryos were deformed, and expression of four transcription factors that control inner ear development declined. As the otic placode invaginates, cells change shape and position. Loss of KDM4B altered the distribution and polarity of proteins, such as E-cadherin and actin, that control cell shape and adhesion to other cells.
Uribe et al. next tried to identify KDM4B’s targets. They discovered that the enzyme binds to and activates the gene encoding the transcription factor DLX3, which had previously been implicated in inner ear development. Adding DLX3 to embryos that lacked KDM4B in their otic ectoderm restored normal otic vesicle formation.
The results indicate that KDM4B promotes invagination of the otic placode by relieving repression of DLX3. The next steps are to determine which genes DLX3 switches on and what controls expression of KDM4B.
Text by Mitch Leslie