Neuron: Find the fateful switch in the retina where the trail is split.

▎ academic longitude / report: fireworks soared into the sky, lighting up the night and the eyes of the audience.thanks to our retina, we can appreciate the thousands of changes of light in an instant.there are nearly a hundred different types of nerve cells in the retina, which are connected to form a complex neural network, rapidly transmit and integrate signals, so that the brain can perceive the magnificent scene of the eyes in real time.Image Source: among these retinal cells, there are some pairs of neurons, one of which responds to the increase of light and the other to the decrease of light, which is crucial for us to perceive the change of light and shade.like looking at a mirror, a pair of cells that look the same but have opposite functions is an interesting and difficult puzzle for developmental biologists.it's just like some people meet a "noble person" when they grow up, which genes will be the key to determine the fate of cells on the road of cell development? In a paper recently published by the authoritative academic journal Neuron, scientists from Harvard University and Johns Hopkins University cooperated to find a switch to control the fate of retinal nerve cells in pairs.in this study, the nerve cells that Dr. Peng Yirong, the first author of this study, and his colleagues paid close attention to, also looked like fireworks, and were named "starburst amacrine cells" (SAC) by neuroscientists.fireworks of the same type may bloom at different heights after liftoff, and this sac cell will also migrate from the birthplace to different positions in the cell layer with the development of the retina.however, the arrangement of life should be more orderly, and the location, structure and function of cells are closely related.a pair of sac cells migrated to the adjacent cell layer, and the neural network was added to respond to enhanced light (on type) and reduced light (off type) respectively.however, apart from the differences in their relative positions, the past methods can hardly distinguish them.therefore, since sac was discovered in the 1970s, they have been considered as a pair of identical cells.} on and off type astroblast amacrine cells (SAC) in mouse retina (photo source: Yi Rong Peng). One of the main leaders of this research team is the famous neuroscientist Professor Joshua R. SANEs, who has made a lot of breakthrough work in the research of retinal cells.earlier this year, the team used a technique called high-throughput single-cell RNA sequencing (scrna SEQ) to create a taxonomic map of retinal cells in primates for the first time.the academic longitude and latitude team has introduced this work to the readers before.so, can this new technology provide more clues to the difference between paired cells? This study gives a beautiful answer.in order to find out the molecular differences between on type sac and off type sac, Dr. Peng Yirong and his colleagues conducted scrna SEQ analysis on more than 2000 sac cells in different development stages, and divided them into two groups according to the difference of gene expression, and determined that the two types with different gene expression profiles were the corresponding on / off types. } the development and change of sac in retina from embryonic stage to postnatal stage (photo source: reference [1]) how to find the key genes that determine different fate from these differentially expressed genes? The researchers speculate that transcription factors regulate the expression of other genes and can control the development process of cells, and if a transcription factor only exists in one group of cells in the early stage of development, it is likely to be the key to guide the cells to their final fate. therefore, researchers focused on finding transcription factors that meet this condition. they found the first target: fezf1. in the early sac cells after the end of mitosis, half of the sac precursor cells expressed this transcription factor. however, at the late stage of development, the half expressing fezf1 migrated to the position close to the inner edge and became on type; on the contrary, the half of cells lacking fezf1 remained at the relative outer edge and became off type. } fezf1 is the key to determine the fate of sac (photo source: reference [1]). A subsequent group of experiments confirmed that fezf1 is the fate switch that controls sac to be on or off! When the researchers removed it from on cells, these cells became off; when they put it in off cells, those cells became on. "this transformation is not only a change of on / off position, but also a complete reversal of on / off gene expression profile. "said Dr. Peng. then, among the various genes regulated by the transcription factor fezf1, are there downstream genes specifically responsible for the migration of on and off cells to different locations? The team went back to the scrna SEQ data and found another gene, Rnd3. and it controls the migration of different sac as part of fezf1 control downstream program. } Rnd3 acts as sac downstream of fezf (photo source: reference [1]). Taking sac of retina as an example, the author combed out a set of gene programs in a haystack to reveal how a pair of similar cells went to different fate. but in our body, there are many other types of neurons. The researchers hope that this method can also effectively identify the key "switches" that determine the structure and function of other neurons, and provide insight into the wonder of life. source: pixabay reference [1] Yi Rong Peng et al. (2019) binary fat choice between closed related internal types is determined by a fezf1 dependent postmitotic translational switch. Neuron. Doi: