IISER Mohali researchers have decoded the different signals and genes behind this feat In stark contrast to mammals, the zebrafish has the ability to completely regenerate its retina and restore vision after an injury. Researchers from Indian Institute of Science Education and Research (IISER) Mohali, have decoded the signals and genes behind this tremendous feat and hope to uncover valuable clues as to why we humans fail at such regeneration. 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.