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Developmental biology

 

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Katja Zscheppang

Project description

 

Surfactant synthesis in preparation for birth is a crucial component of fetal lung development. Insufficient surfactant production by immature type II cells contributes to respiratory distress syndrome (RDS) among preterm infants [Avery et al., Anderson et al.]. The growth factor neuregulin (NRG), a ligand of the erbB receptors 3 and 4, is at least in part responsible for the fetal surfactant synthesis initiating effect [Dammann et al.].

ErbB receptor activation involves the binding of a specific ligand such as NRG. Ligand binding triggers the formation of erbB homo- and heterodimers [Jones et al.]. Different erbB receptor dimers play different roles in different organ systems during development [Gassmann et al.]. We have shown that in fetal lung type II epithelial cells erbB4 and erbB1 appear to be the major communication and dimerization partners [Zscheppang et al., Liu et al.].

We now want to examine the effects of pulmonary erbB4 deletion on lung development in HER4heart mice. The main hypothesis of this study is that deletion of erbB4 will affect lung maturation by down regulating surfactant expression as well as by inhibiting alveolarization. The long term goal of this project is to further characterize the mechanisms by which erbB receptors regulate processes of fetal lung maturation.

 

Methods

 

Isolation of primary cells, Lectin staining, Western Blotting, Electron microscopy, Confocal microscopy

 

References

 

1. Avery ME, Mead J: Surface properties in relation to atelectasis and

hyaline membrane disease. Am J Dis Child 1959, 97:517-523.

 

2. Anderson RN, Kochanek KD, Murphy SL: Report of final mortality statistics,

1995. In: Monthly Vital Statistics Report 1997. vol. vol 45 no 11,supp 2.

Hyattsville, Maryland: National Center for Health Statistics; 1997.

 

3. Dammann CE, Nielsen HC, Carraway KL: Role of Neuregulin1{beta} in the

Developing Lung. Am J Respir Crit Care Med 2003, 167:1711-1716.

 

4. Jones JT, Akita RW, Sliwkowski MX: Binding specificities and affinities of

EGF domains for ErbB receptors. FEBS Lett 1999, 447:227-231.

 

5. Gassmann M, Casagranda F, Orioli D, Simon H, Lai C, Klien R, Lemke G:

Aberrant neural and cardiac development in mice lacking the ErbB4

neuregulin receptor. Nature 1995, 378:390-394.

 

6. Zscheppang K, E. K, Ramadurai SM, Nielsen HC, Dammann CEL: ErbB

receptor cross-talk and co-localization in mouse lung epithelial cells.

Pediatr Res 2004, 55:93A.

 

7. Liu W, Murray S, Nielsen HC, Dammann CEL: ErbB receptor

heterodimerization in fetal rat lung epithelial type II cells and fibroblasts.

Pediatr Res 2004, 55:93A.

 

Supervisor

 

Christiane Dammann

 

V.i.S.d.P: Christiane Dammann, updated: 12.12.2006