Article

Canonical Notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of Clara versus ciliated cell fate

Department of Developmental Biology and Division of Dermatology, Washington University School of Medicine, Box 8103, Saint Louis, MO 63110-1095, USA.
Journal of Cell Science (Impact Factor: 5.43). 01/2010; 123(Pt 2):213-24. DOI: 10.1242/jcs.058669
Source: PubMed

ABSTRACT

Lung development is the result of complex interactions between four tissues: epithelium, mesenchyme, mesothelium and endothelium. We marked the lineages experiencing Notch1 activation in these four cellular compartments during lung development and complemented this analysis by comparing the cell fate choices made in the absence of RBPjkappa, the essential DNA binding partner of all Notch receptors. In the mesenchyme, RBPjkappa was required for the recruitment and specification of arterial vascular smooth muscle cells (vSMC) and for regulating mesothelial epithelial-mesenchymal transition (EMT), but no adverse affects were observed in mice lacking mesenchymal RBPjkappa. We provide indirect evidence that this is due to vSMC rescue by endothelial-mesenchymal transition (EnMT). In the epithelium, we show that Notch1 activation was most probably induced by Foxj1-expressing cells, which suggests that Notch1-mediated lateral inhibition regulates the selection of Clara cells at the expense of ciliated cells. Unexpectedly, and in contrast to Pofut1-null epithelium, Hes1 expression was only marginally reduced in RBPjkappa-null epithelium, with a corresponding minimal effect on pulmonary neuroendocrine cell fate selection. Collectively, the primary roles for canonical Notch signaling in lung development are in selection of Clara cell fate and in vSMC recruitment. These analyses suggest that the impact of gamma-secretase inhibitors on branching in vitro reflect a non-cell autonomous contribution from endothelial or vSMC-derived signals.

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Available from: Zhenyi Liu, Jul 06, 2014
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    • "Notch signalling plays an important role in airway epithelial regeneration. During lung development, Notch signalling is essential for differentiation of the secretory epithelium from proximal lung endoderm[167,168]. In postnatal lung injury, Notch signalling is essential for differentiation of basal cells into secretory cells[107]. "
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    Full-text · Article · Feb 2016 · International Journal of Molecular Sciences
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    • "Notch signaling has an essential role in specification of CCs during lung development [9], [10], [11], [12]. Lineage analysis has shown that airway progenitors that activate Notch signaling during development adopt a CC fate [10]. "
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    Full-text · Article · Feb 2014 · PLoS ONE
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    • "Recently, a pathway that controls MCC development was identified in mouse airway epithelium and X. laevis epidermis. Downregulation of Notch signaling in MCC precursor cells (Tsao et al., 2009; Morimoto et al., 2010) leads to induction of multicilin (Mcin; Mcidas - Mouse Genome Informatics), which functions upstream of centriole amplification and induction of Foxj1 (Stubbs et al., 2012). Although MCIN expression is necessary and sufficient for MCC formation (Stubbs et al., 2012), how this novel nuclear protein controls centriole amplification and later steps in the multiciliogenesis program is not known. "
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