A retinoic acid responsive gene MK found in the teratocarcinoma system is expressed in spatially and temporally controlled manner during mouse embryogenesis.

Abstract

Abstract. A newly identified gene MK is transiently expressed in early stages of retinoic acid-induced differentiation of embryonal carcinoma cells (Kadomatsu, K., M. Tomomura, and T. Muramatsu, 1988. Biochem. Biophys. Res. Commun. 151:1312-1318. MK gene has been predicted to code a polypeptide that is rich in basic amino acids and cysteine and is not related to any other peptides so far reported. In the present study, we investigated MK expression during mouse embryogenesis by in situ hybridization. The MK transcript was detected all over the embryo proper of the 7-d embryo, while it was not detectable in the 5-d embryo. The ubiquitous expression continued in the 9-d embryo proper. On the 1 lth-13th d of gestation, the sites where MK gene was intensely expressed became progressively restricted; these sites were the brain ectoderm around the lens and brain ventricles, the anterior lobe of the pituitary gland, the upper and lower jaw, the caudal sclerotomic half of vertebral column, the limbs, the stomach, and the epithelial tissues of the lung, the pancreas, the small intestine, and the metanephros. These areas include the region where secondary embryonic induction is prominent. In the 15-d embryo, only the kidney expressed MK significantly. These data suggest that MK gene plays a fundamental role in the differentiation of a wide variety of cells; MK gene may also play some specific roles in generation of epithelial tissues, and remodeling of mesoderm.

Midkine induces the transformation of NIH3T3 cells

“…In addition, MK expression is temporally and spatially regulated during embryogenesis: preferential MK expression is observed where epithelial-mesenchymal interactions take place as well as where cells are in proliferative states (e.g. caudal halves of sclerotomes) (Kadomatsu et al, 1990). These data indicate that MK has the potential to play a critical role in both normal and abnormal cell growth and suggest that overexpression of MK may promote unregulated cell growth in vivo.…”

“…Midkine (MK), originally isolated as a product of a retinoic acid-responsive gene in an embryonal carcinoma cell differentiation system, is a heparin-binding growth factor (Kadomatsu et al, 1988;Tomomura et al, 1990 a,b) implicated in neuronal survival and differentiation (Muramatsu and Muramatsu, 1991;Michikawa et al, 1993;Unoki et al, 1994), carcinogenesis (Tsutsui et al, 1993;Nakagawara et al, 1995), fibrinolysis (Kojima et al, 1995), wound healing (Yoshida et al, 1995) and development (Kadomatsu et al, 1990;Mitsiadis et al, 1995a, b). MK belongs to a novel growth factor family whose only members so far are MK and pleiotrophin (PTN)/HB-GAM (Muramatsu, 1993(Muramatsu, , 1994.…”

Immunohistochemical and In Situ Hybridization Analyses of Midkine Expression in Thyroid Papillary Carcinoma

“…MK mRNA expression is quite strong in some organs, such as the brain, stomach, lung, and small intestine, from the 11th to 13th days of gestation (4,5). In adult mice, only the kidney continues to express MK (3-5).…”

“…MK messenger RNA (mRNA) is strongly expressed in various tissues during the midgestation period of mouse embryogenesis (4,5) and it is considered to be involved in regulation of organogenesis in mice (6,7). Although mouse MK mRNA is expressed in the adult kidney, it decreases to undetectable levels with development in all other tissues.…”

The Midkine Family of Growth/ Differentiation Factors

“…On day 15, MK mRNA expression is decreased, except in the kidney. The expression of MK in the kidney persists even in adult mice (9,10); in the kidney its site of expression is the proximal tubules (1 4). lmmunohistochemical studies have in general supported the results obtained by in situ hybridization (32).…”