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Propagation of the proneural wave, in vivo, in the visual system of a developing fruit fly. Credit: Kanazawa University
In biology, the physical differences between organisms of the same type, for example two humans, come from the so-called developmental noise resulting from probabilistic collisions between the molecules in reaction and the environmental conditions in the cells during the early stages of the growth of the cells. organization. In general, mechanisms are in place to prevent biological noise from leading to improper organismic developments. Makoto Sato of Kanazawa University and his colleagues have now discovered that a particular biochemical signaling pathway contributes to the cancellation of noise in the neural stem cell differentiation process – self-renewing cells playing an important role in the development of the nervous system of animals. embryonic stage
As a model system for understanding the mechanisms of biological noise cancellation in a multicellular organism, researchers examined a particular stage of development of the visual system in fruit flies: the propagation of the proneural wave during which Neuroepithelial cells differentiate into neuroblasts (dividing cells into neurons).
Inspired by previous research, Sato and his colleagues hypothesized that a signaling pathway (a particular chain of cell protein responses) called JAK / STAT is involved in noise cancellation. Scientists have combined mathematical modeling and genetic experiments. For the first, they devised a set of mathematical equations that quantify the variations of the system and reproduce the progression of the proneural wave. When they include JAK / STAT signaling, they found that noise-induced spontaneous neuroblastic differentiation is reversed.
To confirm the effect of JAK / STAT signaling in vivo, the researchers performed experiments in which the signaling pathway was reduced in a controlled manner. During the reduction, the stochastic differentiation of neuroblasts was observed, in agreement with the conclusion that JAK / STAT has an anti-noise function. Other genetic experiments have provided more information on the details of noise suppression by JAK / STAT, and this function can be kept throughout the evolution.
The addition of noise causes abnormal differentiation of silico neuroblasts (left), which is effectively suppressed by JAK / STAT (right). Credit: Kanazawa University
Not only does the work of Sato and his colleagues contribute to a better understanding of noise cancellation mechanisms in developmental biology, but they also highlight the power to combine in silico with in vivo studies. Scientists write: "By combining mathematical modeling and molecular genetics, we can solve difficult biological questions."
The reduction of JAK / STAT caused stochastic differentiation of neuroblasts in vivo (right). Credit: Kanazawa University
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More information:
Yoshitaro Tanaka et al, JAK / STAT guarantee a robust differentiation of neural stem cells by blocking biological noise, Scientific reports (2018). DOI: 10.1038 / s41598-018-30929-1
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