(42f) Interpreting Positional Information in the Developing Organ of Corti

The organ of Corti (OC) is the sensory epithelium in the cochlea home to the hair cells that transform sound energy from mechanical vibration to electrochemical signals. The OC’s radial axis is a striking example of precision and reproducibility in biological patterning. Each radial cell in the mature OC has a unique transcriptional identity, even distinguishing among the three rows of outer hair cells, and this pattern is repeated more than 3500 times from the cochlear base to apex. Recent advances in quantitative methods developed against the backdrop of Drosophila gap gene transcription factors (TFs) suggest that cell fate decisions appropriate for their positions are sensitive to precise TF concentrations--a concept deemed optimal decoding. Although the method originated to test data from the Drosophila system, it also reliably predicts locations of Bmp target gene expression in the zebrafish blastula in wild-type and chordin homozygous mutants. This suggests the optimal decoding methodology may be fruitful beyond the fruit fly. To investigate how precise patterning is achieved in the mouse OC, we use these methods to quantitatively characterize strong contributors to positional information present just before and during the onset of cell specification across E12.5-E14.5. Sox2 and phosphorylated smad1/5/9 (P-Smad) are expressed early in development, are dynamically present throughout the process, and have been shown to sensitively influence patterning. Preliminary quantification of positional information in these profiles on E12.5 along the prosensory epithelium reveals a nearly linear P-Smad profile coupled with a nonlinear Sox2 distribution, which appears to be a nearly optimal combination for maximizing information using two profiles. Together at this timepoint, they contain sufficient information to uniquely specify eight subdomains (~3 bits) for the next stage of patterning.