Glial cell line-derived neurotrophic factor promotes the development of adrenergic neurons in mouse neural crest cultures

Abstract

Growth of mouse neural crest cultures in the presence of glial cell line-derived neurotrophic factor (GDNF) resulted in a dramatic dose-dependent increase in the number of tyrosine hydroxylase (TH)-positive cells that developed when 5% chicken embryo extract was present in the medium. In contrast, growth in the presence of bone morphogenetic protein (BMP)-2, BMP-4, BMP-6, transforming growth factor (TGF) ␤1, TGF-␤2, and TGF-␤3 elicited no increase in the number of TH-positive cells. The TH-positive cells that developed in the presence of GDNF had neuronal morphology and contained the middle and low molecular weight neurofilament proteins. Numerous TH-negative cells with the morphology of neurons also were observed in GDNF-treated cultures. Analysis revealed that the period from 6 to 12 days in vitro was the critical time for exposure to GDNF to generate the increase in TH-positive cell number. The growth factors neurotrophin-3 and fibroblast growth factor-2 elicited increases in the number of TH-positive cells similar to that seen in response to GDNF. In contrast, nerve growth factor was unable to substitute for GDNF. These findings extend the previously reported biological activities of GDNF by showing that it can act on mouse neural crest cultures to promote the development of neurons.

Endogenous IGF-1 regulates the neuronal differentiation of adult stem cells

“…A large number of growth factors have been shown to influence neuronal differentiation (Arsenijevic and Weiss, 1998;Bartlett et al, 1995;Kirschenbaum and Goodman, 1995;Lachyankar et al, 1997;Maxwell et al, 1996;Richards et al, 1996;Weisz et al, 1993;Zigova et al, 1998b), and in particular Neurotrophin-3 (NT-3) (Ghosh and Greenberg, 1995), FGF-1 (Bartlett et al, 1998), and low levels of FGF-2 (Qian et al, 1997) have been shown to promote neuronal differentiation of developing forebrain precursors. The response, however, is often small and dependent on conditions that inhibit stem cell proliferation.…”

Glial fibrillary acidic protein (GFAP): modulation by growth factors and its implication in astrocyte differentiation

“…Glial cells, in general, are also involved in providing neurotrophic signals to neurons required for their survival, proliferation and differentiation (13,14). Besides their physiological role, astrocytes play an important role in pathological conditions of the nervous system.…”

Glial Cell Line-Derived Neurotrophic Factor Alters Axon Schwann Cell Units and Promotes Myelination in Unmyelinated Nerve Fibers

“…Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-␤ superfamily, was initially isolated on the basis of its potent trophic effects on midbrain dopaminergic neurons in vitro (Lin et al, 1993, and subsequently was shown to be a potent trophic factor for a subset of sensory neurons as well as for sympathetic and parasympathetic neurons (Buj-Bello et al, 1995;Ebendal et al, 1995;Oppenheim et al, 1995;Trupp et al, 1995;Maxwell et al, 1996;Matheson et al, 1997;Molliver et al, 1997;Bennett et al, 1998). Early in development, all small dorsal root ganglion (DRG) neurons require nerve growth factor (NGF) for survival and express its receptors, trkA and p75.…”