CHONDROITIN SULFATES MODULATE AXON GUIDANCE IN EMBRYONIC XENOPUS BRAIN

Chondroitin sulfate proteoglycans display both inhibitory and stimulat ory effects on cell adhesion and neurite outgrowth in vitro. The funct ional activity of these proteoglycans appears to be context specific a nd dependent on the presence of different chondroitin sulfate-binding molecules. Little is known about the role of chondroitin sulfate prote oglycans in the growth and guidance of axons in vivo. To address this question, we examined the effects of exogenous soluble chondroitin sul fates on the growth and guidance of axons arising from a subpopulation of neurons in the vertebrate brain which express NOC-2, a novel glyco form of the neural cell adhesion molecule N-CAM. Intact brains of stag e 28 Xenopus embryos were unilaterally exposed to medium containing so luble exogenous chondroitin sulfates. When exposed to chondroitin sulf ate, NOC-2(+) axons within the tract of the postoptic commissure faile d to follow their normal trajectory across the ventral midline via the ventral commissure in the midbrain. Instead, these axons either stall ed or grew into the dorsal midbrain or continued growing longitudinall y within the ventral longitudinal tract. These findings suggest that c hondroitin sulfate proteoglycans indirectly modulate the growth and gu idance of a subpopulation of forebrain axons by regulating either matr ix-bound or cell surface cues at specific choice points within the dev eloping vertebrate brain. (C) 1998 Academic Press.