Talk:Respiratory System - Molecular

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Cite this page: Hill, M.A. (2021, September 27) Embryology Respiratory System - Molecular. Retrieved from


Evidence for the involvement of fibroblast growth factor 10 in lipofibroblast formation during embryonic lung development

Development. 2015 Dec 1;142(23):4139-50. doi: 10.1242/dev.109173. Epub 2015 Oct 28.

Al Alam D1, El Agha E2, Sakurai R3, Kheirollahi V2, Moiseenko A2, Danopoulos S1, Shrestha A2, Schmoldt C2, Quantius J2, Herold S2, Chao CM2, Tiozzo C4, De Langhe S5, Plikus MV6, Thornton M7, Grubbs B7, Minoo P8, Rehan VK9, Bellusci S10.


Lipid-containing alveolar interstitial fibroblasts (lipofibroblasts) are increasingly recognized as an important component of the epithelial stem cell niche in the rodent lung. Although lipofibroblasts were initially believed merely to assist type 2 alveolar epithelial cells in surfactant production during neonatal life, recent evidence suggests that these cells are indispensable for survival and growth of epithelial stem cells during adulthood. Despite increasing interest in lipofibroblast biology, little is known about their cellular origin or the molecular pathways controlling their formation during embryonic development. Here, we show that a population of lipid-droplet-containing stromal cells emerges in the developing mouse lung between E15.5 and E16.5. This is accompanied by significant upregulation, in the lung mesenchyme, of peroxisome proliferator-activated receptor gamma (master switch of lipogenesis), adipose differentiation-related protein (marker of mature lipofibroblasts) and fibroblast growth factor 10 (previously shown to identify a subpopulation of lipofibroblast progenitors). We also demonstrate that although only a subpopulation of total embryonic lipofibroblasts derives from Fgf10(+) progenitor cells, in vivo knockdown of Fgfr2b ligand activity and reduction in Fgf10 expression lead to global reduction in the expression levels of lipofibroblast markers at E18.5. Constitutive Fgfr1b knockouts and mutants with conditional partial inactivation of Fgfr2b in the lung mesenchyme reveal the involvement of both receptors in lipofibroblast formation and suggest a possible compensation between the two receptors. We also provide data from human fetal lungs to demonstrate the relevance of our discoveries to humans. Our results reveal an essential role for Fgf10 signaling in the formation of lipofibroblasts during late lung development. © 2015. Published by The Company of Biologists Ltd. KEYWORDS: Fgf10; Lipofibroblasts; Lung; Mesenchyme

PMID 26511927


Lung development: orchestrating the generation and regeneration of a complex organ

Development. 2014 Feb;141(3):502-13. doi: 10.1242/dev.098186.

Herriges M1, Morrisey EE.


The respiratory system, which consists of the lungs, trachea and associated vasculature, is essential for terrestrial life. In recent years, extensive progress has been made in defining the temporal progression of lung development, and this has led to exciting discoveries, including the derivation of lung epithelium from pluripotent stem cells and the discovery of developmental pathways that are targets for new therapeutics. These discoveries have also provided new insights into the regenerative capacity of the respiratory system. This Review highlights recent advances in our understanding of lung development and regeneration, which will hopefully lead to better insights into both congenital and acquired lung diseases. KEYWORDS: Branching morphogenesis; Epigenetics; Lung; Regeneration PMID 24449833


Regulation of early lung morphogenesis: questions, facts and controversies

Development. 2006 May;133(9):1611-24.

Cardoso WV1, Lü J.

Abstract During early respiratory system development, the foregut endoderm gives rise to the tracheal and lung cell progenitors. Through branching morphogenesis, and in coordination with vascular development, a tree-like structure of epithelial tubules forms and differentiates to produce the airways and alveoli. Recent studies have implicated the fibroblast growth factor, sonic hedgehog, bone morphogenetic protein, retinoic acid and Wnt signaling pathways, and various transcription factors in regulating the initial stages of lung development. However, the precise roles of these molecules and how they interact in the developing lung is subject to debate. Here, we review early stages in lung development and highlight questions and controversies regarding their molecular regulation. PMID 16613830