Slits are chemorepellents endogenous to hypothalamus and steer thalamocortical axons into ventral telencephalon.
Thalamocortical axons (TCAs) originate in dorsal thalamus, extend ventrally along the lateral thalamic surface, and as they approach hypothalamus make a lateral turn into ventral telencephalon. In vitro studies show that hypothalamus releases a chemorepellent for TCAs, and analyses of knockout mice indicate that Slit chemorepellents and their receptor Robo2 influence TCA pathfinding. We show that Slit chemorepellents are the hypothalamic chemorepellent and act through Robos to steer TCAs into ventral telencephalon. During TCA pathfinding, Slit1 and Slit2 are expressed in hypothalamus and ventral thalamus and Robo1 and Robo2 are expressed in dorsal thalamus. In collagen gel cocultures of dorsal thalamus and Slit2-expressing cells, axon number and length are decreased on the explant side facing Slit2-expressing cells, overall axon outgrowth is diminished, and axons turn away from the Slit2-expressing cells. Thus, Slit2 is an inhibitor and chemorepellent for dorsal thalamic axons. Collagen gel cocultures of dorsal thalamus with sections of live diencephalon, with and without the hypothalamus portion overlaid with Robo2-fc-expressing cells to block Slit function, identify Slits as the hypothalamic chemorepellent. Thus, Slits are chemorepellents for TCAs endogenous to hypothalamus and steer TCAs from diencephalon into ventral telencephalon, a critical pathfinding event defective in Slit and Robo2 mutant mice.
Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA 92037, USA.
Janet E
JE
Braisted
Thomas
T
Ringstedt
Dennis D M
DD
O'Leary
D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D019521:Body Patterning / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013687:Telencephalon / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D013788:Thalamus
D006023:Glycoproteins; D009419:Nerve Tissue Proteins; C120566:slit protein, vertebrate