Slit1 and Slit2 cooperate to prevent premature midline crossing of retinal axons in the mouse visual system

Neuron. 2002 Jan 17;33(2):219-32. doi: 10.1016/s0896-6273(01)00586-4.


During development, retinal ganglion cell (RGC) axons either cross or avoid the midline at the optic chiasm. In Drosophila, the Slit protein regulates midline axon crossing through repulsion. To determine the role of Slit proteins in RGC axon guidance, we disrupted Slit1 and Slit2, two of three known mouse Slit genes. Mice defective in either gene alone exhibited few RGC axon guidance defects, but in double mutant mice a large additional chiasm developed anterior to the true chiasm, many retinal axons projected into the contralateral optic nerve, and some extended ectopically-dorsal and lateral to the chiasm. Our results indicate that Slit proteins repel retinal axons in vivo and cooperate to establish a corridor through which the axons are channeled, thereby helping define the site in the ventral diencephalon where the optic chiasm forms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / physiology*
  • Diencephalon / embryology
  • Embryonic and Fetal Development / physiology
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Mice, Knockout / genetics
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neural Inhibition / physiology
  • Optic Chiasm / embryology
  • Preoptic Area / embryology
  • Retina / embryology*
  • Retinal Ganglion Cells / physiology
  • Synaptic Transmission / physiology
  • Visual Pathways / embryology*


  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Slit1 protein, mouse
  • Slit homolog 2 protein