Protein phosphatase 1α is required for murine lung growth and morphogenesis

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Abstract
Protein phosphatase 1 (PP1) plays important roles in cell cycle control and apoptosis, two processes that impinge on morphogenesis and differentiation. Following the precedent set by other molecules regulating the cell cycle and apoptosis, we hypothesized that PP1 may have context‐specific roles in development. Therefore, we have studied the spatial and temporal expression of PP1α during murine lung development and determined the consequences of loss of PP1α function on branching morphogenesis. By using an immunohistochemical approach, we show here that PP1α was expressed throughout the epithelium and mesenchyme upon the emergence of the lung primordium on embryonic day 10, with immunostaining exclusively extranuclear. During the late pseudoglandular stage, PP1α was predominantly expressed in the distal lung epithelium, whereas the mesenchyme contained very little or no PP1α protein. Peri‐ and postnatally, PP1α immunostaining was mostly nuclear in apparently differentiated cells, as judged by colocalization with well‐known markers for lung differentiation. Exposure of fetal lung explants to antisense oligodeoxynucleotides against PP1α, resulted in decreased overall size of the cultured lung, a defect in forming new airways, lack of expression of surfactant protein C, and histologic signs of poor differentiation. These data suggest that PP1α is required for branching morphogenesis and differentiation. Developmental Dynamics 229:791–801, 2004.