User:Kaleinonen/sandbox

Structural realism has evolved from realism.

Function
'''The binding of Slit to Robo receptors leads to reorganization of the actin cytoskeleton. Actin polymerization is regulated by several adaptor proteins that can bind to the cytoplasmic motifs of the Robo receptors. In Drosophila, several signaling proteins downstream of Robo1 have been identified, including Cross GTPase-activating protein (CrossGAP), son of sevenless (SOS), Rac, and Dock.[15][16][17][18] It is thought that activation of Robo1 by Slit leads to increased depolymerization of actin, resulting in growth cone collapse. It remains unclear how Drosophila Robo2 and Robo3 signal, although multiple studies suggest that they have distinct signaling capabilities that cannot be recapitulated by Robo1.[19][19] In the developing nervous system of vertebrates, Robo1 and Robo2 share a conserved requirement for triggering Slit-mediated repulsion in axons. However, Robo3/Rig1 has evolved a novel function: it is alternatively spliced to generate a protein that inhibits Robo1/2-mediated repulsion, effectively leading to the promotion of midline crossing. The mechanism by which Robo3 achieves this anti-repulsive activity is unknown.[20]'''

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Discovery
In 1993 Seeger et al performed an experiment with hopes of discovering the genes involved in axonal guidance. Seeger et al exposed Drosophila to mutagens, and those exhibiting axonal guidance defects were studied. A large-scale screening of the Drosophila that exhibited axonal guidance defects led to the discovery of the roundabout mutation. The roundabout mutation caused developing axons to cross and recross the midline. In 1999, Kidd et al found that axons in which the roundabout gene product, a receptor, was highly expressed, axons failed to cross midline. In axons that failed to express the Robo receptor, axons crossed the midline multiple times. In commissural axons, high levels of Robo were found to be expressed only after the axon had crossed the midline. Experimental results suggested that Robo gene products are receptors that aid in axonal projection repulsion from the midline.

Introduction
Robo, or roundabout, refers to a highly conserved gene family that encodes a series of receptors found in growing axonal projections. Robo receptors act as a repulsive force when bound to a Slit(add internal link) ligand, playing a key role in axon guidance(add internal link). In Drosophila, three Robo homologs have been discovered, Robo 1, Robo 2, and Robo 3. In vertebrates, four Robo genes have been discovered, Robo1, Robo2, Robo3, and Robo4. Vertebrate Robo1 and Robo2 are highly homologous in function to Drosophila Robo1.

Types of Robo
In Drosophila, three Robo homologs have been discovered, Robo 1, Robo 2, and Robo 3. In vertebrates, four Robo genes have been discovered, Robo1, Robo2, Robo3, and Robo4. Vertebrate Robo1 and Robo2 are highly homologous in function to Drosophila Robo1.

Function
Robo gene products are thought to be activated upon the binding of a Slit ligand.[1] Within cell cultures the Robo/Slit complexes have been observed to repel embryonic spinal nerves, suggesting that Robo genes may aid in directing and shaping the branching of the nervous system through development.[citation]

=The Role of Robo in the Mechanism of Axonal Repulsion= Normal axonal growth and nervous system development requires the crossing of axonal projections across the midline. In Drosophila, normal axonal midline crossing requires netrin (link to the page on netrin, if there is one), commissureless (Comm) protein, and a Robo gene product bound to Slit ligand. (Guthrie, mice and men need rig and robo.) As an axonal projection grows, it is attracted to the midline by netrin. During the phase of axonal projection growth prior to midline crossing, Robo receptors are mediated by commisureless protein and are localized in the cytoplasm of the axon. Limiting the of Robo receptor to the cytoplasm inhibits its repellent nature. As the axonal projection crosses the midline, the inhibition of Robo by the midline commisureless protein diminishes. Robo receptors then translocate to the cell surface, which allows the binding of Slit and mediates repulsion of the growing axon.

Robo genes have also been proposed to have tumor suppressor functions.

Within Drosophila, Robo gene products have been observed to play a role in the development of the reproductive organs, blood vessels, and heart.[citation]