Regulation of taste bud cell differentiation by notch signaling pathway.

The Notch pathway is involved in determining cell fate within the nervous system and in various sensory organs (Lanford et al., 1999; Cau et al., 2000; Furukawa et al., 2000; Ito et al., 2000; Zine et al., 2000). For example, Mash1 is expressed in subsets of neuronal precursors in both the central nervous system (CNS) and the peripheral nervous system (PNS) (Guillemot et al., 1993). Disruption of the Mash1 gene in mice results in the elimination of most olfactory and autonomic neurons, showing a role for Mash1 in the development of particular neural lineages (Guillemot et al., 1993). In addition, Mash1 promotes differentiation during retinal development and is essential for proper ratios of neural cell types (Tomita et al., 1996). Recently, Mash1 has been shown to be expressed in cells of the taste bud lineage, and that the expression of Mash1 in rat taste buds is dependent upon gustatory innervation (Seta et al., 1999). However, involvement of the Notch signaling pathway, except for Mash1, in taste bud cell differentiation remained to be demonstrated. In the present study, to begin to understand the mechanisms that regulate taste bud cell differentiation in fetal lingual epithelia, we have investigated the expression patterns of Notch and its ligands, Delta-like 1 (Dll1) and Jaggeds, hairy/enhancer of split (Hes1), and a mammalian homolog of the achaete-scute complex (Mash1) in fetal and adult mouse tongues using in situ hybridization. These genes are expressed in complex, dynamic patterns both in developing taste papillae and in taste cells within adult taste buds. The timing and pattern of early Notch signaling expression suggests a role for these genes in either sharpening the borders of developing papillae and/or specifying taste bud progenitors within papillae. Expression of Notch pathway genes in mature taste buds suggests that this signaling system may function in cell lineage decisions within taste buds.