Project description:The cochlear duct is tonotopically organized, such that the basal cochlea responds more sensitively to high frequency sounds and the apical cochlea to low frequency sounds. In effort to understand how the tonotopic organization is established in mammals, we searched for genes that are differentially expressed along the tonotopic axis during neonatal development.
Project description:The cochlear duct is tonotopically organized, such that the basal cochlea responds more sensitively to high frequency sounds and the apical cochlea to low frequency sounds. In effort to understand how the tonotopic organization is established in mammals, we searched for genes that are differentially expressed along the tonotopic axis during neonatal development. Eighty temporal bones were dissected from C57BL/6 mice at P0 and P8. The cochlear tissues were divided into three equal pieces representing the basal, middle and apical turns, and pooled separately. Six total RNA from the pooled samples were applied to 6 GeneChips.
Project description:In the mammalian auditory system, frequency discrimination depends on numerous morphological and physiological properties of the organ of Corti that gradually change along the longitudinal (tonotopic) axis of the organ. For example, the basilar membrane stiffness changes tonotopically, thus affecting the tuning properties of individual hair cells. At the molecular level, those frequency-specific characteristics are mirrored by gene expression gradients; however, the molecular mechanisms controlling tonotopic gene expression in the mouse cochlea remain elusive. Through analyzing scRNA-seq data from two developmental time points, we predicted that morphogens, rather than a timing-associated mechanism, confer spatial identity in the cochlea. Subsequently, we reconstructed the developing cochlea in 3D space from scRNA-seq data to investigate the molecular pathways mediating tonotopic information. The retinoic acid and sonic hedgehog pathways were found to form opposing tonotopic gradients, and functional interrogation using mouse cochlear explants suggested that both pathways jointly specify the tonotopic axis during development.
Project description:The role of the hippocampus in learning and memory has been widely studied. However, studies of differences along the longitudinal axis indicate that the hippocampus is perhaps not a singular structure, but instead it is thought that the dorsal and ventral poles of the hippocampus have functional differences. An anatomical gradient of hippocampal inputs along the dorsal-ventral axis supports this notion. It has been recently shown that there is transcriptional differentiation along the longitudinal axis of the adult hippocampus, coinciding with functional and anatomical gradients. Understanding the development of the dorsal-ventral hippocampal axis will further our understanding of the different hippocmapal functional contributions along the longitudinal axis. However, analysis of transcriptional gradients along the dorsal ventral axis have not been studied in the neonatal rat during development. We performed an extensive bead-chip based geneome-wide analysis of transcriptional differences in dorsal, intermediate, and ventral hippocampal tissue of rats aged postnatal day 0 (P0), P9, P18 and P60.