Restricted Expression of Xenopus Midkine Gene during Early Development1

Abstract

Midkine (MK) is a heparin-binding growth factor and forms a novel protein family together with another member, pleiotrophin (PTN)/heparin-binding growth-associated molecule (HB-GAM). A cDNA clone isolated from Xenopus laevis specifies for the Xenopus counterpart of MK (XMK), and the mode of XMK expression was studied by in situ hybridization and Northern blot analysis. XMK was first expressed at stage 11 (middle gastrula) and was located in the neural anlage at stage 12 (late gastrula). Through stage 13 to 15 (early neurula), XMK expression was restricted to the neural folds. At stage 23 (tailbud stage), XMK was predominantly localized in the brain and neural tube. At the larva stage, XMK expression was again restrictedly observed in the brain, the optic vesicles, the otic vesicle, and the spinal cord, all of which are derivatives of the neural tube, as well as in the branchial arches, derivatives of the cranial neural crest. Comparing the mode of MK expression between Xenopus and the mouse, we propose that MK plays evolutionally conserved roles in neurogenesis and development of the craniofacial architecture of ectomesenchymal origin. We also found that XMK was expressed in various adult organs; strong expression was observed in the brain, the eye and the spinal cord, all of which showed intense MK expression at the larva stage.

Dimerization of Midkine by Tissue Transglutaminase and Its Functional Implication

“…As Factor XIIIa is larger than tissue transglutaminase (ϳ300 kDa versus 80 kDa), the cross-linking of MK molecules may not be performed by Factor XIIIa, even though it can stimulate putrescine incorporation into MK molecules. It is notable that these three acyl-donating Gln residues are conserved among the MK/ PTN family, whereas the other two Gln residues are not (48). As can be seen in Fig.…”

Midkine Binds to Anaplastic Lymphoma Kinase (ALK) and Acts as a Growth Factor for Different Cell Types

“…10 and 11). MK modulates epithelial-mesenchymal interactions during fetal development and organogenesis in the mouse (12) as well as in Xenopus (13). From in vitro cell biology studies and the embryonic expression pattern of MK in the central nervous system it was concluded that MK directs neurite interconnections during an early phase of brain development and may later on have a maintenance function in some restricted areas.…”

Molecular Characterization of Xenopus Embryo Heparan Sulfate

“…Furthermore, elimination of HS-PG by heparitinases induced abnormal mesodermal differentiation. Embryogenesis is thought to be regulated by signaling factors, such as FGFs (7), bone morphogenetic proteins (8,9), activin (10,11), midkine (12), hepatocyte growth factor (13), Vg1 (14), Wnt (15,16) and Sonic Hedgehog (17), which are expressed in early stages in Xenopus embryogenesis. Since most of these growth factors have a heparin (HP)/HS binding property, at least some of these signaling factors, probably exert their functions during embryogenesis through interactions with HS-PG.…”