Hey2 functions in parallel with Hes1 and Hes5 for mammalian auditory sensory organ development
1 Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA
2 University of Washington School of Medicine at SLU, 815 Mercer Street, Seattle, WA 98109, USA
BMC Developmental Biology 2008, 8:20 doi:10.1186/1471-213X-8-20Published: 26 February 2008
During mouse development, the precursor cells that give rise to the auditory sensory organ, the organ of Corti, are specified prior to embryonic day 14.5 (E14.5). Subsequently, the sensory domain is patterned precisely into one row of inner and three rows of outer sensory hair cells interdigitated with supporting cells. Both the restriction of the sensory domain and the patterning of the sensory mosaic of the organ of Corti involve Notch-mediated lateral inhibition and cellular rearrangement characteristic of convergent extension. This study explores the expression and function of a putative Notch target gene.
We report that a putative Notch target gene, hairy-related basic helix-loop-helix (bHLH) transcriptional factor Hey2, is expressed in the cochlear epithelium prior to terminal differentiation. Its expression is subsequently restricted to supporting cells, overlapping with the expression domains of two known Notch target genes, Hairy and enhancer of split homolog genes Hes1 and Hes5. In combination with the loss of Hes1 or Hes5, genetic inactivation of Hey2 leads to increased numbers of mis-patterned inner or outer hair cells, respectively. Surprisingly, the ectopic hair cells in Hey2 mutants are accompanied by ectopic supporting cells. Furthermore, Hey2-/-;Hes1-/- and Hey2-/-;Hes1+/- mutants show a complete penetrance of early embryonic lethality.
Our results indicate that Hey2 functions in parallel with Hes1 and Hes5 in patterning the organ of Corti, and interacts genetically with Hes1 for early embryonic development and survival. Our data implicates expansion of the progenitor pool and/or the boundaries of the developing sensory organ to account for patterning defects observed in Hey2 mutants.