scholarly journals A model for reticular dysgenesis shows impaired sensory organ development and hair cell regeneration linked to cellular stress

2019 ◽  
Vol 12 (12) ◽  
pp. dmm040170 ◽  
Author(s):  
Alberto Rissone ◽  
Erin Jimenez ◽  
Kevin Bishop ◽  
Blake Carrington ◽  
Claire Slevin ◽  
...  
Keyword(s):  
Hair Cell ◽  
Cellular Stress ◽  
Sensory Organ ◽  
Cell Regeneration ◽  
Organ Development ◽  
Hair Cell Regeneration

scholarly journals A model for reticular dysgenesis shows impaired sensory organ development and hair cell regeneration linked to cellular stress

2019 ◽  
Author(s):  
Alberto Rissone ◽  
Erin Jimenez ◽  
Kevin Bishop ◽  
Blake Carrington ◽  
Claire Slevin ◽  
...  
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Therapeutic Option ◽  
Sensory Organ ◽  
Therapeutic Modality ◽  
Cell Regeneration ◽  
Organ Development ◽  
Hair Cell Regeneration ◽  
Sensory Hair ◽  
Sensory Hair Cells

AbstractMutations in the gene AK2 are responsible for Reticular Dysgenesis (RD), a rare and severe form of primary immunodeficiency in children. RD patients have a severely shortened life expectancy and without treatment die a few weeks after birth. The only available therapeutic option for RD is bone marrow transplantation. To gain insight into the pathophysiology of RD, we previously created zebrafish models for an AK2 deficiency. One of the clinical features of RD is hearing loss, but its pathology and causes have not been determined. In adult mammals, sensory hair cells of the inner ear do not regenerate; however, their regeneration has been observed in several non-mammalian vertebrates, including zebrafish. Therefore, we use our RD zebrafish models to determine if AK2 deficiency affects sensory organ development and/or hair cell regeneration. Our studies indicated that AK2 is required for the correct development, survival and regeneration of sensory hair cells. Interestingly, AK2 deficiency induces the expression of several oxidative stress markers and it triggers an increased level of cell death in the hair cells. Finally, we show that glutathione treatment can partially rescue hair cell development in the sensory organs in our RD models, pointing to the potential use of antioxidants as a supportive therapeutic modality for RD patients, not only to increase their chances of survival, but to prevent or ameliorate their sensorineural hearing deficits.

Hair cell regeneration in the inner ear

1994 ◽  
Vol 111 (3) ◽  
pp. 281-301 ◽  
Author(s):  
T TSUE ◽  
E OESTERLE ◽  
E RUBEL
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Cell Regeneration ◽  
Hair Cell Regeneration

Hair-cell regeneration: cure for deafness?

The Lancet ◽  
1995 ◽  
Vol 346 (8971) ◽  
pp. 325-326 ◽  
Author(s):  
KarenP. Steel
Keyword(s):  
Hair Cell ◽  
Cell Regeneration ◽  
Hair Cell Regeneration

Delta1 expression during avian hair cell regeneration

Development ◽  
1999 ◽  
Vol 126 (5) ◽  
pp. 961-973 ◽  
Author(s):  
J.S. Stone ◽  
E.W. Rubel
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Cell Injury ◽  
Basilar Papilla ◽  
Cell Regeneration ◽  
Mrna Levels ◽  
Hair Cell Regeneration ◽  
Drug Induced ◽  
In Cells

Postembryonic production of hair cells, the highly specialized receptors for hearing, balance and motion detection, occurs in a precisely controlled manner in select species, including avians. Notch1, Delta1 and Serrate1 mediate cell specification in several tissues and species. We examined expression of the chicken homologs of these genes in the normal and drug-damaged chick inner ear to determine if signaling through this pathway changes during hair cell regeneration. In untreated post-hatch chicks, Delta1 mRNA is abundant in a subpopulation of cells in the utricle, which undergoes continual postembryonic hair cell production, but it is absent from all cells in the basilar papilla, which is mitotically quiescent. By 3 days after drug-induced hair cell injury, Delta1 expression is highly upregulated in areas of cell proliferation in both the utricle and basilar papilla. Delta1 mRNA levels are elevated in progenitor cells during DNA synthesis and/or gap 2 phases of the cell cycle and expression is maintained in both daughter cells immediately after mitosis. Delta1 expression remains upregulated in cells that differentiate into hair cells and is downregulated in cells that do not acquire the hair cell fate. Delta1 mRNA levels return to normal by 10 days after hair cell injury. Serrate1 is expressed in both hair cells and support cells in the utricle and basilar papilla, and its expression does not change during the course of drug-induced hair cell regeneration. In contrast, Notch1 expression, which is limited to support cells in the quiescent epithelium, is increased in post-M-phase cell pairs during hair cell regeneration. This study provides initial evidence that Delta-Notch signaling may be involved in maintaining the correct cell types and patterns during postembryonic replacement of sensory epithelial cells in the chick inner ear.

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