Localization of cells synthesizing transforming growth factor-alpha mRNA in the mouse brain

Abstract

The distribution of transforming growth factor (TGF)-alpha and TGF-beta 1 mRNA containing cells in adult mouse brain was examined using in situ hybridization histochemistry. There were no detectable TGF-beta 1 mRNA-containing cells found in the brain. TGF-alpha mRNA was localized to cell bodies of the caudate nucleus, dentate gyrus, anterior olfactory nuclei, and a laminar distribution of mitral cells in the olfactory bulb. TGF-alpha-synthesizing cells were localized in brain regions that have been shown to synthesize nerve growth factor, epidermal growth factor (EGF) and enkephalins. The function of local synthesis of TGF-alpha in the brain is as yet unknown.

Transforming Growth Factor-α Null and Senescent Mice Show Decreased Neural Progenitor Cell Proliferation in the Forebrain Subependyma

“…TGF␣-dependent proliferation of constitutively proliferating progenitors may be contingent on their location in the dorsolateral corner. The relatively restricted domain of normal TGF␣ expression in rostral, dorsal regions of the forebrain (Wilcox and Derynck, 1988;Seroogy et al, 1993) may elicit a proliferative response only in those rostral, dorsolateral subependymal cells destined to migrate to the olfactory bulbs. The lack of a proliferation deficit in the constitutively proliferating progenitors throughout the remaining subependyma in the TGF␣ null mice suggests that other growth factors expressed in the nondorsolateral subependyma (ventrolateral and medial), especially EGF expression in more caudal and ventral regions such as the globus pallidus (Fallon et al, 1984;Seroogy et al, 1995), may regulate the proliferation of cells in this spatially distinct part of the forebrain subependyma.…”

“…Two candidates for the endogenous regulation of cell proliferation are epidermal growth factor (EGF) and transforming growth factor-␣ (TGF␣). TGF␣ mRNA has been localized to the adult striatum and olfactory bulbs, both of which are in close apposition to the forebrain subependyma (Wilcox and Derynck, 1988;Seroogy et al, 1993). Conversely, EGF mRNA is localized to relatively ventrocaudal forebrain regions in the adult, such as the globus pallidus, with apparently little expression near the subependyma (Fallon et al, 1984;Seroogy et al, 1995).…”

Involvement of transforming growth factor alpha in the release of luteinizing hormone-releasing hormone from the developing female hypothalamus.

“…Nevertheless, the inability to detect authentic EGF and the very low levels of EGF mRNA found throughout the brain (5, 7) suggest that in vivo EGF actions may be shared by another, more abundant endogenous constituent of the brain. A likely candidate for this role is TGF-a, which shares 35% sequence homology with EGF, interacts with the same receptor (30), and is produced by brain cells (3,4,8). Although some evidence already exists supporting this concept (31), little (if anything) is known regarding the ability of EGF and/or TGF-a to affect mature, differentiated functions of specific neuronal subpopulations.…”

“…Although the brain has been shown to contain an EGF immunoreactive material (1), not all of this substance(s) may correspond to authentic EGF, as judged by the inability of a specific two-site immunoassay to detect the peptide (6) and by the electrophoretic behavior of the cross-reacting substance, which differs substantially from that of EGF (7). In contrast, recent reports have unambiguously demonstrated the presence of both TGF-a and its mRNA in mammalian brain (3,4,8,9).…”

Serotonin and Hippocampal Neurogenesis

“…Recent evidence indicates that a significant percentage of the precursor population in the adult dentate gyrus expresses EGF receptors (EGFr) (Okano et al 1996). Moreover, TFG ␣ is produced at relatively high levels in the adult dentate gyrus and appears to be synthesized by neurons (Wilcox and Derynck 1988;Seroogy et al 1991). These findings present the possibility that EGF or TGF ␣ is the endogenous factor that directly stimulates the proliferation of granule cell precursors.…”