Background Previously, we reported that Sema3A, one of the secreted repulsive axon guidance molecules, CRMP (collapsin response mediator protein)‐2, a putative intracellular signalling molecule for Sema3A and Sema3A receptor neuropilin‐1 are expressed in the developing lung. Sema3A inhibits branching morphogenesis of embryonic lung in organ culture. Results We examined the gene expression of Sema3A, Sema3C, Sema3F and their receptors, NP‐1, NP‐2 and plexin‐A1 by in situ hybridization. Transcripts of all six genes were detected in mouse lung from embryonic day E11.5 to E17.5, and displayed highly specific spatiotemporal distributions. The distribution of the receptor genes was detected in patterns which were consistent with known receptor usage of the semaphorins. In contrast to Sema3A, we found that the other class 3 semaphorins, Sema3C and Sema3F, stimulated branching morphogenesis. This stimulatory effect of Sema3C or Sema3F was accompanied by a moderate increase in the incorporation of bromodeoxyuridine (BrdU) into DNA in the terminal epithelial cells. Conclusion The coordinated expression patterns of different semaphorins and their receptors, together with the specific activities affecting branching morphogenesis, suggest that the semaphorins act as both positive and negative regulators of branching morphogenesis in the developing lung.
Hepatocyte growth factor (HGF) is a mesenchymal‐derived factor which induces mitosis, cell movement and morphogenesis of tissue‐like structure. We analyzed changes in HGF mRNA and its receptor, the c‐ met proto‐oncogene product, in the liver, kidney and lung during late fetal and postnatal development in rats. In the liver, the HGF‐mRNA level was very low during late gestation and in neonates, it increased remarkably and reached a maximum two weeks postnatally, to be followed by a decrease to 33% of the maximum. HGF mRNA in the kidney and lung was either undetectable or very low during late gestation and the neonatal period and increased markedly to reach a maximum, respectively, 3–4 weeks postnatally. HGF‐mRNA level in the adult rat lung was fivefold higher than that in the liver and kidney. The number of HGF receptors on plasma membranes of these tissues was low in neonates but there was a rapid increase after birth and a maximum was reached within three weeks. The number of HGF receptors/ng plasma membrane protein at the maximal level was highest in the liver and lowest in the lung. c‐ met /HGF‐receptor mRNA in the liver was also low during late‐gestation or in early neonatal periods and increased postnatally. Since HGF‐mRNA and HCF‐receptor levels changed differently in liver, kidney and lung, the expression of HGF and its receptor may be independently regulated in each organ. However, in these organs, HGF mRNA and the HGF receptor increased within a few weeks of birth, HGF may play roles in organ growth, organ maturation and the maintenance of tissue homeostasis during the postnatal period, presumably through its potential to act as mitogen, motogen and morphogen.
'/%3e%3cpath d='M200 752.362h200v300H200z' style='fill:%23fff;fill-opacity:1;stroke:none' transform='translate(0 -752.362)'/%3e%3cpath d='M400 752.362h200v300H400z' style='fill:%23ff883e;fill-opacity:1;stroke:none' transform='translate(0 -752.362)'/%3e%3c/svg%3e)