By Christopher Geissler, Ph.D., and Cardiff University
Scientists have learned an incredible amount since the discovery three decades ago that some animal species are able to regenerate hair cells, but they are still only beginning to understand the genes and signaling involved in tissue regeneration. In a Sept. 25, 2019, article published in the Annual Review of Cell and Developmental Biology, Hearing Restoration Project (HRP) consortium member Tatjana Piotrowski, Ph.D., and colleagues at the Stowers Institute for Medical Research in Missouri summarize the existing literature on hair cell regeneration in the context of sensory cell regeneration more broadly.
While there are many similarities in the development and regeneration of sensory cell types (those involved in vision, for example), recent research has highlighted significant differences. Cross-species comparisons are an important means of identifying these differences, which is why this approach is central to the HRP’s work. Studies suggest, for example, that the limited success that has been experienced in regenerating support cells in mammals may be because these cells are more differentiated in mammals than the analogous cells in zebrafish, a species that can regenerate.
Zebrafish lateral line cells are homologous to mammalian inner ear hair cells, but they detect water movement instead of sound in order to preserve their ability to orient themselves. Credit: Jane G Photography.
The researchers identify the key question researchers in the field need to answer to significantly advance their efforts: “Which signal or signals trigger hair cell regeneration?” There are numerous hypotheses about the mechanisms through which dying sensory cells signal the need for repair and regeneration, including molecular triggering of the immune system and inflammation.
Work in the field thus far indicates that in spite of numerous differences, the molecular response that drives stem cell activation is fundamentally similar. In spite of the fact that early efforts to regenerate mammalian hair cells have resulted in modest numbers of hair cells that fail to survive, there is sufficient promise that a better understanding of so-called downstream signaling pathways, which scientists hypothesize are typically epigenetically silenced in postnatal mammals, will prove key to moving beyond these preliminary results.
In a separate study, Piotrowski and colleagues at Stowers and Cardiff University in the U.K. investigated the genes underlying two cell signaling pathways—PCP and Wnt—that are present in both humans and zebrafish and are known to affect the way in which sensory hair cells in the cochlea coordinate their orientations.
Hair cells are “tuned” to respond to different sounds based on pitch or frequency. This is due to a collective property called planar polarization, or the orientation in which the hair cells are laid out. When sound enters the ear, the hair cells change the sound vibrations into an electrical signal that is sent to the brain, allowing us to recognize it. Genetic factors are thought to cause more than 50 percent of all incidents of congenital hearing loss, with many attributed to the misalignment of or damage to hair cells.
Using zebrafish as a proxy, the team systematically switched off these genes in the zebrafish and were able to study the effects on hair cell direction. As published in Nature Communications on Sept. 6, 2019, the results showed that not only could the regularity of the hair cell pattern be destroyed, producing a random hair cell direction, but certain alterations to the genes could lead to the hair cells having circular or spiral patterns.
A portion of this was adapted from a press release from Cardiff University on EurekAlert. HRP consortium member Tatjana Piotrowski, Ph.D., is an associate investigator at the Stowers Institute for Medical Research in Missouri.
For more information about the HRP, see hhf.org/hrp.
You can make a donation to support top-tier scientists like those of the HRP. HHF maintains stellar charity ratings from all watchdogs and pledges to use your gift wisely.
