Cells undergo complex changes in morphology and gene expression as they differentiate, but the relationship between these changes has long been obscure, with hints that cell shape per se can control cellular patterns of gene expression in some cases. Yang et al. now offer a novel example of such control, as well as welcome insights into its molecular basis. Smooth muscle cell precursors become stretched as fluid accumulates in the lumen of the developing lung, and the authors show that this mechanical deformation is sufficient to induce the expression of several differentiation-dependent smooth muscle cell proteins. Stretching of cells, whether they are plated in 2 dimensions on an elastic membrane or maintained in 3 dimensions in organ culture, induces mRNAs for smooth muscle a actin and other gene products that are under control of the transcription factor serum response factor (SRF). SRF is alternatively spliced to generate an active isoform and a dominant negative isoform called SRFD5, both of which are expressed in smooth muscle cell precursors. Yang and colleagues show stretch rapidly alters this splicing pattern such that only the active isoform is generated, thus inducing the expression of SRF target genes. After analyzing lung tissue from human infants who had died perinatally with hypoplastic lungs, the authors conclude that the same pathway exists in human lung development. They suggest that low intrapulmonary hydrostatic pressure, as occurs in fetuses with oligohydramnion, prevents the cellular shape change that allows for normal smooth muscle myogenesis in the lung.

'"/>

Contact: John Ashkenas
scied@the-jci.org
206-221-5690
Journal of Clinical Investigation
28-Nov-2000