Hesr1 and Hesr2 may act as early effectors of Notch signaling in the developing cochlea
| Autor: | Thomas A. Reh, Byron H. Hartman, Toshinori Hayashi, Catherine A. Ray, Olivia Bermingham-McDonogh, Hiroki Kokubo |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Cellular differentiation
Gene Expression Cell Cycle Proteins Hey1 Hey2 Hydroxamic Acids Mice 0302 clinical medicine Lateral inhibition Inner ear Basic Helix-Loop-Helix Transcription Factors Morphogenesis Serrate-Jagged Proteins Mice Knockout 0303 health sciences Receptors Notch Gene Expression Regulation Developmental Cell Differentiation Dipeptides Cell biology Cochlea medicine.anatomical_structure Hey3 Intercellular Signaling Peptides and Proteins Hair cell Signal Transduction JAG1 Notch Notch signaling pathway Biology Article Prosensory 03 medical and health sciences Organ Culture Techniques Hair Cells Auditory medicine Animals Hesr3 HEY2 Molecular Biology 030304 developmental biology Calcium-Binding Proteins Membrane Proteins Cell Biology Repressor Proteins Jagged-1 Protein 030217 neurology & neurosurgery Gene Deletion Developmental Biology |
| Zdroj: | Developmental Biology. 316(1):87-99 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2008.01.006 |
| Popis: | In cochlear development, the Notch signaling pathway is required for both the early prosensory phase and a later lateral inhibition phase. While it is known that Hes genes are important downstream mediators of Notch function in lateral inhibition, it is not known what genes function as mediators of the early prosensory function of Notch. We report that two members of the Hes-related gene family, Hesr1 and Hesr2, are expressed in the developing cochlea at a time and place that makes them excellent candidates as downstream mediators of Notch during prosensory specification. We also show that treatment of cochlear explant cultures at the time of prosensory specification with a small-molecule inhibitor of the Notch pathway mimics the results of conditional Jag1 deletion. This treatment also reduces Hesr1 and Hesr2 expression by as much as 80%. These results support the hypothesis that Hesr1 and Hesr2 are the downstream mediators of the prosensory function of Notch in early cochlear development. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect