Repulsive axon guidance molecule Sema3A inhibits branching morphogenesis of fetal mouse lung

被引:81
作者
Ito, T
Kagoshima, M
Sasaki, Y
Li, CX
Udaka, N
Kitsukawa, T
Fujisawa, H
Taniguchi, M
Yagi, T
Kitamura, H
Goshima, Y
机构
[1] Yokohama City Univ, Sch Med, Dept Pharmacol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
[2] Yokohama City Univ, Sch Med, Dept Pathol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan
[3] Nagoya Univ, Grad Sch Sci, Div Biol Sci, Grp Dev Neurobiol,Chikusa Ku, Nagoya, Aichi 4648602, Japan
[4] Univ Tokyo, Grad Sch Med, Dept Biochem & Mol Biol, Tokyo 1100033, Japan
[5] Natl Inst Physiol Sci, Dept Neurobiol & Behav Genet, Okazaki, Aichi 444, Japan
[6] JST, Japan Sci & Technol Corp, CREST, Kawaguchi 3320012, Japan
基金
日本学术振兴会;
关键词
branching morphogenesis; lung; Sema3A; neuropilin-1; CRMP-2;
D O I
10.1016/S0925-4773(00)00401-9
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Semaphorin III/collapsin-1 (Sema3A) guides a specific subset of neuronal growth cones as a repulsive molecule. In this study, we have investigated a possible role of non-neuronal Sema3A in lung morphogenesis. Expression of mRNAs of Sema3A and neuropilin-1 (NP-1), a Sema3A receptor, was detected in fetal and adult lungs. Sema3A-immunoreactive cells were found in airway and alveolar epithelial cells of the fetal and adult lungs. Immunoreactivity for NP-1 was seen in fetal and adult alveolar epithelial cells as well as endothelial cells. Immunoreactivity of collapsin response mediator protein CRMP (CRMP-2), an intracellular protein mediating Sema3A signaling, was localized in alveolar epithelial cells, nerve tissue and airway neuroendocrine cells. The expression of CRMP-2 increased during the fetal, neonate and adult periods, and this pattern paralleled that of NP-1. In a two-day culture of lung explants from fetal mouse lung (E11.5), with exogenous Sema3A at a dose comparable to that which induces growth cone collapse of dorsal root ganglia neurons, the number of terminal buds was reduced in a dose-dependent manner when compared with control or untreated lung explants. This decrease was not accompanied with any alteration of the bromodeoxyuridine-positive DNA-synthesizing fraction. A soluble NP-1 lacking the transmembrane and intracellular region, neutralized the inhibitory effect of Sema3A. The fetal lung explants from neuropilin-1 homozygous null mice grew normally in vitro regardless of Sema3A treatment, These results provide evidence that Sema3A inhibits branching morphogenesis in lung bud organ cultures via NP-I as a receptor or a component of a possible multimeric Sema3A receptor complex. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:35 / 45
页数:11
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