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How brain cells reach their target

How do developing brain cells connect with their intended target? And how do they maintain that connection over a life-span? Research from The University of Texas Medical Branch (UTMB) in Galveston, Texas can now shed some light on these mysteries.


The brain contains regions that serve specific functions such as interpreting sensory information, controlling body movement, memory formation, and so on. In order for these regions to interact and perform complex tasks, the brain operates and maintains a web of interconnecting pathways.

A study by Krishna M. Bhat PhD, UTMB professor in the department of neuroscience and cell biology, along with his team show that a protein called Slit is required for maintaining these interconnecting pathways. Without continual guidance from Slit, these pathways even those important to communication between brain regions after birth can drift off course.

The research findings are published in the journal Science Signaling.

The study found that Slit keeps brain cells on their paths in partnership with receptor proteins called Robo. The study also observed that Slit-Robo signaling is controlled by an enzyme called Mummy, which modifies Slit so that it can be secreted outside of the cell in which it is made. In this way Mummy can affect other cells on the pathway while still maintaining a correct distribution of Robo in neural cells through early and late nervous system development.
"Although Slit-Robo signaling is intensely studied, [research] emphasis has always been on understanding the events controlling the beginning of the process guiding developing brain circuits to their destinations.

"Here, we show that Slit-Robo signaling is required not only at the intial stages of brain circuitry guidance, but also later for maintaining those networks of circuits. This has implications for loss of cognition and other brain functions as we age and/or in many neuro-diseases."


Krishna M. Bhat PhD, Professor, Department of Neuroscience and Cell Biology, Univeristy of Tesas Medical Branch, Galveston, Texas, USA

Glycosylation and axon guidance The secreted protein Slit is a repulsive axon guidance cue that binds to the receptor Roundabout (Robo). Manavalan et al. report that Mummy (Mmy), an enzyme of the glycosylation pathway, regulated the Slit-Robo signaling pathway in the developing nervous system of Drosophila melanogaster. In mmy mutants, Slit was not secreted from the midline cells of the ventral nerve cord, resulting in axon guidance defects. In addition, Mmy was also required for maintaining Robo abundance and distribution in axons. Thus, glycosylation affects axon tract establishment and maintenance through mechanisms that affect both the ligand and the receptor.

Abstract
Slit proteins act as repulsive axon guidance cues by activating receptors of the Roundabout (Robo) family. During early neurogenesis in Drosophila melanogaster, Slit prevents the growth cones of longitudinal tract neurons from inappropriately crossing the midline, thus restricting these cells to trajectories parallel to the midline. Slit is expressed in midline glial cells, and Robo is present in longitudinal axon tracts and growth cones. We showed that the enzyme Mummy (Mmy) controlled Slit-Robo signaling through mechanisms that affected both the ligand and the receptor. Mmy was required for the glycosylation of Slit, which was essential for Slit secretion. Mmy was also required for maintaining the abundance and spatial distribution of Robo through an indirect mechanism that was independent of Slit secretion. Moreover, secretion of Slit was required to maintain the fasciculation and position of longitudinal axon tracts, thus maintaining the hardwiring of the nervous system. Thus, Mmy is required for Slit secretion and for maintaining Robo abundance and distribution in the developing nervous system in Drosophila.

Other authors include UTMB's Mary Ann Manavalan, Vatsala Ruvini Jayasinghe and Rickinder Grewal.


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Jun 29, 2017   Fetal Timeline   Maternal Timeline   News   News Archive




This study was conducted on the fruitfly, Drosophila, whose brain pathfinding mechanisms
are remarkably similar to humans during fetal development.
Image Credit: Wikipedia.org



Phospholid by Wikipedia