Ž . Developmental Brain Research 102 1997 299–303 Short communication Expression of HGF and cMet in the developing and adult brain C.L. Achim ) , S. Katyal, C.A. Wiley, M. Shiratori, G. Wang, E. Oshika, B.E. Petersen, J.-M. Li, G.K. Michalopoulos UniÕersity of Pittsburgh School of Medicine, Department of Pathology, Pittsburgh, PA 15213, USA Accepted 10 June 1997 Abstract Ž . Hepatocyte growth factor HGF was recently recognized as a potential neurotrophic factor in the developing brain. We studied expression of HGF and its receptor using Northern blot analysis and in situ hybridization for mRNA and double immunofluorescent laser confocal microscopy. HGF and cMet messages were abundant in the hippocampus of both human and rat brains. In this region, both messages were localized in the neuronal layer. Segregation of HGF predominantly in the hippocampal CA3–4 and cMet in CA1 supports the hypothesis that HGF may mediate important neurotrophic functions in both developing and adult brains. q 1997 Elsevier Science B.V. Keywords: Hepatocyte growth factor; cMet; Brain; In situ hybridization Ž . Hepatocyte growth factor HGF was first described as a serum factor whose levels increased following hepatec- wx tomy 7 . Based on its mitogenic activity demonstrated in vitro, HGF was initially proposed as a growth factor for w x hepatocytes 8,10,19 . More recently, numerous other ac- tivities have been associated with HGF and its in vivo functions are proposed to go well beyond the originally w x described liver regeneration 14,18 . HGF is produced predominantly by stromal cells and acts on epithelial cells. The importance of this mesenchy- mal–epithelial interaction is obvious during fetal develop- w x ment 9,12,13 . The activities of HGF in the adult organ- ism are less well described but extrapolation from develop- mental studies suggests that in addition to mitogenic and motogenic properties, HGF may control morphogenesis following injury. A comprehensive review of HGF and its receptor cMet functions was recently published by Zarnegar and w x Michalpoulos 18 . Among these, of relevance to our study is the distribution of HGF and its receptor in the central Ž . w x nervous system CNS 2,15,16,20 . Compared to other ) Corresponding author. PUH-A515, Division of Neuropathology, 200 Ž . Lothrop St., Pittsburgh, PA 15213, USA. Fax: q1 412 647-5468; E-mail: achim@np.awing.upmc.edu organs, some studies suggest that cMet is selectively ex- wx pressed in cells of monocytic origin like microglia 3. These data are intriguing since a paracrine relationship between neurons and microglia would be the reverse of previously shown stromal epithelial interaction in other organs. Many observations of HGFrcMet expression in the CNS are contradictory. Developmental and postnatal ex- pression of HGF and its receptor have been described in a limited number of studies of the murine CNS. Most au- thors agree that HGF, a potentially neurotrophic factor Ž . NTF , may be differentially expressed in the developing mammalian brain. For these reasons, we studied by in situ Ž . hybridization ISH regional expression of HGF and cMet in the rat brain during the first 4 postnatal weeks and compared it to the adult brain. In addition, we compared Ž . the murine findings with results of Northern blot NB analysis of autopsy human brain material. Ž . Two rats Sprague–Dawley, Hilltop for each time point Ž . studied newborn, day 28 and adult were killed by barbi- turate overdose and the brains were immediately frozen and stored at y708C. Ten m m thick para-sagittal sections including hippocampus were cut on aminopropyltri- ethoxysilane-coated slides and fixed in 4% paraformal- dehyde. The slides were rinsed in phosphate-buffered Ž . saline, treated with proteinase K 1 mgrml and acetylated 0165-3806r97r$17.00 q 1997 Elsevier Science B.V. All rights reserved.