ErbB receptors in fetal lung development
Neuregulin1 (NRG1) is a critical component of mesenchymal induced type II cell maturation. NRG signals its effect on surfactant synthesis in the fetal type II cells via ErbB receptors. (1-5). We have shown that inhibition of ErbB4 in fetal rat lung type II cells led to a decrease in fetal surfactant synthesis (6). The main hypothesis of the proposed study is that deletion of ErbB4 or ErbB2 in the fetal lung will affect lung maturation by affecting surfactant expression and alveolarization.
Surfactant protein expression and alveolarization will be studied on HER4heart, (7) HER2heartmice (8).
Immunohistochemistry, In situ hybridization, Stereology, Western Blotting, Light and electron microscopy.
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4. Dammann CE, Ramadurai SR, McCants D, Pham LD, Nielsen HC. Androgen regulation of signalling pathways in late fetal mouse lung development Endocrinology 2000 141: 2923-29.
5. Van Schaik SM, Nielsen HC, Carraway KL, Pham LD, Volpe MV, Dammann CEL. ErbB receptors in late fetal lung development. Pediatr Res 2000; 47:68A.
6. Zscheppang K, Liu W, Volpe MV, Nielsen HC, Dammann CEL. ErbB4 Regulates Fetal Surfactant Synthesis (submitted).
7. Tidcombe, H., A. Jackson-Fisher, et al. (2003). "Neural and mammary gland defects in ErbB4 knockout mice genetically rescued from embryonic lethality." PNAS 100(14): 8281-8286.
8. Woldeyesus, M. T., S. Britsch, et al. (1999). "Peripheral nervous system defects in erbB2 mutants following genetic rescue of heart development." Genes Dev. 13(19): 2538-2548.
V.i.S.d.P: Christiane Dammann, updated: 12.12.2006