Division of Neurobiology , Cornell University Medical College , New York , New York 10021 .
J Neurosci 9 : 3529-37 ( 1989)
Abstract
We sought to determine the source of the signal(s ) that promotes expression of the catecholamine ( CA ) enzyme tyrosine hydroxylase ( TH ) in cultured neurons of embryonic rat cerebral cortex , a tissue which is not thought to contain CA cells in vivo .
Cortical neurons were cultured with their non-neuronal constituents and 48 hr later immunostained for TH .
Fibroblasts or glia had no effects , however , blood vessels increased the numbers of TH neurons nearly 4-fold .
Coculture with either perinatal aorta , skeletal or cardiac muscle , clonal muscle cell lines ( smooth ) and L6 ( skeletal ) , conditioned media from L6 cells , or a soluble extract of L6 cells increased the number of TH neurons up to -fold .
The induction of TH by muscle extract was ( 1 ) dose dependent ; ( 2 ) paralleled by a proportional increase in the steady-state levels of TH mRNA ; ( 3 ) greatly reduced by the RNA synthesis inhibitor alpha-amanitin or the protein synthesis inhibitor cycloheximide ; and ( 4 ) unassociated with change in the survival of neurons in culture .
The response was not replicated by treatment with other established neurotrophic substances , including NGF , EGF , FGF , PDGF , neuroleukin , insulin , pyruvate , KCI , adenosine , or inosine .
We conclude that muscle contains a potentially novel substance , muscle-derived differentiation factor ( MDF ) that promotes differentiation but not survival of neurons of cerebral cortex by de novo synthesis of TH mRNA and TH protein .
Thus , neurons of the CNS , as in periphery , may undergo phenotypic interconversion in response to biologically derived molecules in their environment .