PUBLICATION

Guided genetic screen to identify genes essential in the regeneration of hair cells and other tissues

Authors
Pei, W., Xu, L., Huang, S.C., Pettie, K., Idol, J., Rissone, A., Jimenez, E., Sinclair, J.W., Slevin, C., Varshney, G.K., Jones, M., Carrington, B., Bishop, K., Huang, H., Sood, R., Lin, S., Burgess, S.M.
ID
ZDB-PUB-180607-7
Date
2018
Source
NPJ Regenerative medicine   3: 11 (Journal)
Registered Authors
Burgess, Shawn, Huang, Haigen, Jimenez, Erin, Lin, Shuo, Pei, Wuhong, Sood, Raman, Varshney, Gaurav, Xu, Lisha
Keywords
none
MeSH Terms
none
PubMed
29872546 Full text @ NPJ Regen Med
Abstract
Regenerative medicine holds great promise for both degenerative diseases and traumatic tissue injury which represent significant challenges to the health care system. Hearing loss, which affects hundreds of millions of people worldwide, is caused primarily by a permanent loss of the mechanosensory receptors of the inner ear known as hair cells. This failure to regenerate hair cells after loss is limited to mammals, while all other non-mammalian vertebrates tested were able to completely regenerate these mechanosensory receptors after injury. To understand the mechanism of hair cell regeneration and its association with regeneration of other tissues, we performed a guided mutagenesis screen using zebrafish lateral line hair cells as a screening platform to identify genes that are essential for hair cell regeneration, and further investigated how genes essential for hair cell regeneration were involved in the regeneration of other tissues. We created genetic mutations either by retroviral insertion or CRISPR/Cas9 approaches, and developed a high-throughput screening pipeline for analyzing hair cell development and regeneration. We screened 254 gene mutations and identified 7 genes specifically affecting hair cell regeneration. These hair cell regeneration genes fell into distinct and somewhat surprising functional categories. By examining the regeneration of caudal fin and liver, we found these hair cell regeneration genes often also affected other types of tissue regeneration. Therefore, our results demonstrate guided screening is an effective approach to discover regeneration candidates, and hair cell regeneration is associated with other tissue regeneration.
Genes / Markers
Figures
Figure Gallery (10 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fh229
    Point Mutation
    hg76
      Small Deletion
      hg77
        Small Deletion
        hg78
          Small Deletion
          hg79
            Small Deletion
            hg80
              Small Deletion
              hg81
                Small Deletion
                hg99
                  Small Deletion
                  hg100
                    Small Deletion
                    hg101
                      Small Deletion
                      1 - 10 of 26
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Fish
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CFPEFGCFP
                      NTREFGNTR
                      1 - 2 of 2
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                      Mapping
                      No data available