Proprioceptor pathway development is dependent on MATH1

The proprioceptive system provides continuous positional information on the limbs and body to the thalamus, cortex, pontine nucleus, and cerebellum. W e showed previously that the basic helix-loop-helix transcription factor Ma th1 is essential for the development of certain components of the proprioce ptive pathway, Including inner-ear hair cells, cerebellar granule neurons, and the pontine nuclei. Here, we demonstrate that Math1 null embryos lack t he D1 interneurons and that these interneurons give rise to a subset of pro prioceptor interneurons and the spinocerebellar and cuneocerebellar tracts. We also identify three downstream genes of Math1 (Lh2A, Lh2B, and Barhl1) and establish that Math1 governs the development of multiple components of the proprioceptive pathway.