Gene Environmental Coordination of Post-Embryonic Neuronal Maturation

I attended a talk on Gene Environmental Coordination of Post-Embryonic Neuronal Maturation, by HaoSheng Sun, an assistant professor at the University of Alabama in Birmingham. He studies evolutionary mechanisms in the brain in an attempt to understand species specific solutions that organisms have come up with and the underlying biology. Specifically, he talked about post-embryonic neuronal maturation. Neurodevelopment begins in the embryo, but neurons still undergo post-mitotic changes that affect connectivity and communication a lot. An experiment where a cat had one eye sewn shut early on in life demonstrated that the limitation of sensory input let to defects in neuronal maturation—the environment plays a key role in post-mitotic neuronal maturation. Professor Sun did his studies in the c. elegans, since it has exactly 302 neurons that are perfectly identified and lineaged. He then studied the worm’s locomotion using automated software analysis and organized the data into phases of life, from birth to adulthood.

An important neuropeptide, NLP-45 was tracked closely by the software and it was found that the amount of the gene increased over time. This was related to the Lin-4/Lin-14 pathway, since they regulated NLP-45. Specifically, NLP-45 upregulation caused the worm’s behavior to change to that of an L1 control mouse, which is a very specific phase of the worm’s lifecycle. Usually, LIN-4 was downregulated in L1 and then upregulated in mature adults, and LIN-4 expression was correlated with NLP-45 expression. The NLP gene was related to anti-exploratory activity, which makes sense; when the c. elegans is a child, it is evolutionarily expedient to have it not explore much and stay safe while it grows. As it reaches adulthood, NLP-45 expression, and the correlated exploratory behavior, would increase, making the worm more curious. The pathway Dr. Sun discovered was as follows: LIN-4/mIR-125 (a transcription factor complex) inhibited LIN-14 which inhibited NLP-45. Low NLP-45 levels led to anti-exploratory activity. They further found that sex and environment both had an impact; sex related genes like TRA-1 and environment related genes like DAF-15 both acted as transcription factors to increase and inhibit LIN-14 expression respectively, demonstrating sexually dimorphic exploratory behavior.

A separate focus on the collected data found that the AIB interneuron was important for controlling forward/reverse locomotion. The expression of LIN-4 would reduce over development in the AIB interneuron, thus releasing more NLP-45 over the course of the worm’s life cycle and increasing locomotion and exploration. The study was overall interesting and very well conducted, with a hyper specific focus on transcription factors and the related neurochemistry.

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