IISER
Mohali researchers have decoded the different signals and genes behind this
feat
A particular
signalling system — sonic hedgehog (Shh) — in zebrafish has been previously
reported to aid in developmental and tissue regeneration activities. To
decipher the influence of Shh signalling on retina regeneration, the
researchers first inhibited its function. They found that impairing this signal
made 90% of the zebrafish embryo exhibit a birth defect called cyclopia.
Cyclopia is also seen in humans, where there is a single median eye or a
partially divided eye. Detailed understanding of this signalling may provide
insights into the rare defect. Since this signalling is also responsible for
retina regeneration in zebrafish, the researchers are trying to understand why
the signalling does not bring about retina regeneration in humans.
They performed
whole retina RNA sequencing at various time points post-retinal injury to the
zebrafish eye. Several genes (zic2b, foxn4, mmp9) were found to be upregulated
through Shh signalling. Zic2b and foxn4 are essential components for
development and tissue regeneration, whereas mmp9 is an enzyme which makes the
environment congenial for freshly formed cells. Individual knockdowns of these
genes also revealed that these are indeed essential for normal retina
regeneration.
The researchers
also showed the role of a microRNA (let-7) which is regulated through a
particular gene (Lin28a) which allows normal Shh signalling during the retina
regeneration process. “During an injury, you need the proliferation of cells
that let-7 is capable of blocking. So Lin28a steps in action, clears or
scavenges let-7 and allows differentiated cells to be transformed into
multipotent stem cells, which aid in regeneration,” explains Rajesh
Ramachandran from the Department of Biological Sciences at the Institute and
corresponding author of the work published in the journal Cell Reports.
Mice
models
They further
carried out studies on mice models by injecting the protein. “Shh protein can
easily bind to its respective receptor and turn on the signalling pathway after
an acute retinal injury,” says Simran Kaur, PhD scholar and first author of the
work. “Though there was increased proliferation and upregulation of the genes,
no regeneration of the retina was seen in mice.”
“Although we
have understood the signals and genes behind the regeneration, the whole
pathway and network need to be unravelled before trying it out in the mammalian
system,” adds Prof. Rajesh.
Source: THE HINDU-17th September,2018
