Protocadherin‐17 function in Zebrafish retinal development

Abstract

Cadherin cell adhesion molecules play crucial roles in vertebrate development including the development of the retina. Most studies have focused on examining functions of classic cadherins (e.g. N-cadherin) in retinal development. There is little information on the function of protocadherins in the development of the vertebrate visual system. We previously showed that protocadherin-17 mRNA was expressed in developing zebrafish retina during critical stages of the retinal development. To gain insight into protocadherin-17 function in the formation of the retina, we analyzed eye development and differentiation of retinal cells in zebrafish embryos injected with protocadherin-17 specific antisense morpholino oligonucleotides (MOs). Protocadherin-17 knockdown embryos (pcdh17 morphants) had significantly reduced eyes due mainly to decreased cell proliferation. Differentiation of several retinal cell types (e.g. retinal ganglion cells) was also disrupted in the pcdh17 morphants. Phenotypic rescue was achieved by injection of protocadherin-17 mRNA. Injection of a vivo-protocadherin-17 MO into one eye of embryonic zebrafish resulted in similar eye defects. Our results suggest that protocadherin-17 plays an important role in the normal formation of the zebrafish retina.

The hyaloid vasculature facilitates basement membrane breakdown during choroid fissure closure in the zebrafish eye

“…Indeed, multiple N-cadherin mutants exist in zebrafish that present with colobomas (Liu et al, 2001; Erdmann et al, 2003; Masai et al, 2003) although the cell biological mechanisms leading to these defects have not yet been resolved. Other cadherins expressed in the zebrafish eye include R-cadherin (Liu et al, 1999a; Liu et al, 1999b; Babb et al, 2005), cadherin 6 (Liu et al, 2008), and protocadherin 9 and 17 (Liu et al, 2009; Chen et al, 2013b), and these could also play a role in tissue fusion during CFC. Finally, the rapid turnover of β-catenin within the CF presents an excellent model to study how formation and maintenance of adherens junctions are regulated in vivo.…”

The Transcriptomics of Glucocorticoid Receptor Signaling in Developing Zebrafish

“…These pathways include neurogenesis, cardiovascular development, angiogenesis, and organogenesis [ 41 ], and protocadherin-2 also affects neurogenesis in human fetal models [ 42 ]. Among the protocadherin genes with significantly affected expression in this study, protocadherin-17 is the best studied and interestingly, it is expressed prominently in the eye, and its knockdown results in reduced cell proliferation in the retina [ 43 ]. There is also further evidence for disrupted eye formation in GR morphant embryos, as the two connexin genes that are significantly upregulated at both timepoints, cx23 and cx44.1 ( Table 4 ), are both expressed in the embryonic zebrafish eye [ 44 , 45 ].…”

A single-cell guide to retinal development: Cell fate decisions of multipotent retinal progenitors in scRNA-seq

“…Other genes, including Pcdh17 , Gadd45a, Gadd45g, and Btg2, function as tumor suppressors in numerous tissues ( el Ghissassi et al, 2002 ; Hollander and Fornace, 2002 ; Hu et al, 2013 ; Hwang et al, 2020 ; Vairapandi et al, 2002 ; Yuniati et al, 2019 ) and therefore, may display enriched expression within neurogenic RPCs in order to promote cell cycle exit. In zebrafish, knock-down of pcdh17 via morpholino injection resulted in smaller eyes with reduced mitotic divisions and reduced cell differentiation, suggesting that pcdh17 may in fact regulate cell cycle exit within RPCs ( Chen et al, 2013 ).…”