Slit (protein)

Slit is a family of secreted extracellular matrix proteins which play an important signalling role in the neural development of most bilaterians (animals with bilateral symmetry).

[1] The ventral midline of the central nervous system is a key place where axons can either decide to cross and laterally project or stay on the same side of the brain.

The Slit protein is produced and secreted by cells within the floor plate (in vertebrates) or by midline glia (in insects) and diffuses outward.

[4] Slit mutations were first discovered in the Nuesslein-Volhard/Wieschaus patterning screen where they were seen to affect the external midline structures in the embryos of Drosophila melanogaster, also known as the common fruit fly.

In this experiment, researchers screened for different mutations in D. melanogaster embryos that affected the neural development of axons in the central nervous system.

Slit genes, as well as their roundabout receptors, act as chemorepellents by helping prevent the wrong types of axons from crossing the midline of the central nervous system during establishment or remodeling of the neural circuits.

Slit2 begins the formation of axon branches through neural growth factor genes of the dorsal root ganglia.

Several studies have shown that the interaction of Slit with its receptors is crucial in regulating the processes involved with the formation of organs.

Not surprisingly then, this gene has been found expressed during the development of tightly regulated tissues, such as the heart, lungs, gonads, and ovaries.

For example, in early development of the heart tube in Drosophila, Slit and two of its Robo receptors guide migrating cardioblasts and pericardial cells in the dorsal midline.

It has been concluded that the role of Slit in this process depends on which receptor it binds, the cellular context of its target cells, and/or other environmental factors.

[11] Procedures have been found in which Slit genes allow for precise control over vascular guidance cues influencing the organization of blood vessels during development.

[15] Due to its pivotal role in controlling cell migration, abnormalities or absences in the expression of Slit1, Slit2 and Slit3 are associated with a variety of cancers.

Samples of surface epithelium in cancer ridden ovaries has exhibited that these cells show decreased expression of Slit2 and Slit3.