The brains of all higher order animals are filled with a diverse array of neuron types, with specific shapes and functions. Yet, when these brains form during embryonic development, there is initially only a small pool of cell types to work with. So how do neurons diversify over the embryo’s development? Researchers know that neural stem cells called neuroblasts divide multiple times to sequentially produce neurons of specialized function, but the mechanisms of this process, and how the timing varies for different genes and neuron types, is still not fully understood.
Alokananda Ray, a postdoctoral researcher in the Li lab (left) with Xin Li, an assistant professor of cell and developmental biology. Image credit: Julia Pollack
n a new paper published in eLife, Alokananda Ray, a Ph.D candidate during the time of the study and now graduated, and Xin Li (GNDP), an assistant professor of cell and developmental biology at the University of Illinois Urbana-Champaign, shed light on the process in the optic medulla of Drosophila melanogaster, the fruit fly.
As neuroblasts divide and differentiate, they express transcription factors which ultimately direct the daughter cells on what kind of neuron to be. Because they are expressed in a particular way depending on when they split, these transcription factors, called temporal transcription factors, act as a marker that tells researchers what stage the neuroblast is at, and allows them to piece together the order of events in this neurogenesis cascade. The researchers focused on two different TTFs in the fruit fly brain, called eyeless and sloppy-paired, to better understand how differences in the expression of TTFs that lead to different neuron fates.
“Nervous systems diversify from a small pool of neural stem cells to the great diversity of neurons we see in adult brains of higher ordered animals,” said Ray. “We really wanted to understand the molecular mechanisms that drive the transition of these neuroblasts from expressing one temporal transcription factor to the next transcription factor, which ultimately determines what type of neurons these progenies will become.”
The researchers discovered that two non-coding regions near the sloppy-paired genes were essential to making sure the sloppy-paired TTFs expressed at the right time and amount. Researchers then removed these non-coding DNA regions, called enhancers, using the gene-editing technique CRISPR to see how the brain of the flies were affected, and found that flies with deleted enhancers showed a complete absence of expression of the sloppy-paired TTF in medulla neuroblasts.