EXPRESSION, LOCALIZATION, AND FUNCTION OF TRANSFORMING GROWTH FACTOR-BETA-S IN EMBRYONIC CHICK SPINAL-CORD, HINDBRAIN, AND DORSAL-ROOT GANGLIA

We have studied the localizations of transforming growth factor-beta ( TGF-beta)2 and 3 immunohistochemically using isoform-specific antibodi es and TGF-beta 3 mRNA by in situ hybridization in the nervous system of the 3- to 15-day-old chick embryo with special reference to spinal cord, hindbrain, and dorsal root ganglia (DRG). At embryonic day (E) 3 , TGF-beta 3 mRNA as well as TGF-beta 2 and 3 immunoreactivities (IRs) were most prominent in the notochord, wall of the aorta, and dermomyo tome. At E5 and E7, strong TGF-beta 2 and 3 IR were seen in or on radi al glia of spinal cord and hindbrain. Radial glia in the floor plate r egion and ventral commissure gave the most intense signal. In the DRG, fiber strands of intense IRs representing extracellular matrix or sat ellite cells were seen, Neuronal perikarya did not become IR for TGF-b eta 2 and 3 until E11, but even then the moderate signals for TGF-beta 3 mRNA could not be specifically localized to the neuronal cell bodie s. In E11 and older embryos, spinal cord glial or glial progenitor cel ls, but not neuronal cell bodies were labeled for TGF-beta 3 mRNA. Imm unocytochemistry and western blot analysis indicated that E8 DRG neuro ns have the TGF-beta receptor type II, and treatment of these cells wi th NGF induces expression of TGF-beta 3 mRNA. The TGF-beta isoforms 1, 2, and 3 did not promote survival of E8 DRG neurons in dissociated ce ll cultures. All three TGF-beta isoforms, however, promoted neurite gr owth from E8 DRG explants, but were less potent than nerve growth fact or. Our data suggest identical localizations of TGF-beta 2 and -beta 3 IR in the developing chick and mammalian nervous systems, underscorin g the general importance of TGF-beta s in fundamental events of neural , development. (C) 1996 John Wiley & Sons, Inc.