FGF10 maintains distal lung bud epithelium and excessive signaling leads to progenitor state arrest, distalization, and goblet cell metaplasia

<p>Abstract</p> <p>Background</p> <p>Interaction with the surrounding mesenchyme is necessary for development of endodermal organs, and Fibroblast growth factors have recently emerged as mesenchymal-expressed morphogens that direct endodermal morphogenesis. The fibroblast growth factor 10 (<it>Fgf10</it>) null mouse is characterized by the absence of lung bud development. Previous studies have shown that this requirement for <it>Fgf10 </it>is due in part to its role as a chemotactic factor during branching morphogenesis. In other endodermal organs <it>Fgf10 </it>also plays a role in regulating differentiation.</p> <p>Results</p> <p>Through gain-of-function analysis, we here find that FGF10 inhibits differentiation of the lung epithelium and promotes distalization of the embryonic lung. Ectopic expression of FGF10 in the lung epithelium caused impaired lung development and perinatal lethality in a transgenic mouse model. Lung lobes were enlarged due to increased interlobular distance and hyperplasia of the airway epithelium. Differentiation of bronchial and alveolar cell lineages was inhibited. The transgenic epithelium consisted predominantly of proliferating progenitor-like cells expressing Pro-surfactant protein C, TTF1, PEA3 and Clusterin similarly to immature distal tip cells. Strikingly, goblet cells developed within this arrested epithelium leading to goblet cell hyperplasia.</p> <p>Conclusion</p> <p>We conclude that FGF10 inhibits terminal differentiation in the embryonic lung and maintains the distal epithelium, and that excessive levels of FGF10 leads to metaplastic differentiation of goblet cells similar to that seen in chronic inflammatory diseases.</p

Effect of a proline analogue, azetidine-2-carboxylic acid, on the morphogenesis <i>in vitro</i> of mouse embryonic lung

ABSTRACT A proline analogue, azetidine-2-carboxylic acid, which has been reported to selectively depress collagen biosynthesis, affects lung morphogenesis in vitro by determining differential modifications of the rate of epithelial growth and ramification activity. Low concentrations of the analogue induce a sharp decline of the number of newly formed terminal buds, leaving the rate of global growth of the epithelial tree almost unaffected. This effect is reversed by increasing doses which appear more effective on global epithelial growth than on budding. DNA and protein content at the end of the treatment are unequally reduced. Protein concentration is more depressed with consequent rise of the DNA/protein ratio. These results show that epithelial budding is very sensitive to the treatment with the analogue, and draw attention to collagen biosynthesis as one of the possible mechanisms by which the mesenchyme controls the spatial organization of the epithelial tree. This type of control appears relatively independent on the actual rate of epithelial cell replication, since budding is much more sensitive to the action of the drug.</jats:p

Esercizi, Quiz e Problemi di Biologia Generale della Cellula

La pubblicazione consiste in una sequenza di 12 capitoli, ciascuno dei quali dedicato ad una specifica tematica di Biologia Cellulare che viene brevemente riassunta nei suoi concetti essenziali. Ciascun capitolo contiene test di autovalutazione per lo studente articolati nelle sezioni: frasi ad incastro, caccia all'errore, domande a scelta multipla e problemi, per ognuna delle quali, capitolo per capitolo, sono fornite le risposte corrette e le opportune spiegazioni. Il testo costituisce un possibile utile complemento all'uso di un testo base utilizzabile per l'apprendimento delle conoscenze teoriche necessarie in un corso di Biologia Cellulare di valenza universitaria

Biologia generale e molecolare della cellula

La pubblicazione consiste in un trattato di Biologia diretto principalmente agli studenti di Medicina che può essere valido supporto anche per la preparazione di Corsi di Biologia cellulare per gli studenti di Scienze Biologiche e per i Corsi di studio di Biotecnologie Interfacoltà (Medicina, Scienze e Farmacia). Il testo è organizzato in due parti. La prima parte consta di 7 capitoli: 1) Lo stato vivente della materia, 2) Organizzazione della materia vivente nelle unità biologiche elementari, 3) La informazione biologica, 4) La storia della vita sulla Terra, 5) La dinamica della vita. Le basi molecolari, 6) Complessità e versatilità delle macromolecole, 7) La dinamica della vita. La seconda parte consta di 9 capitoli: 1) La membrana plasmatica: individualità e socialità della cellula, 2) Struttura e organizzazione dell’apparato genetico, 3) Dal genotipo al fenotipo: il braccio efferente del circuito informativo, 4) Organizzazione generale del citoplasma. 5) La compartimentalizzazione intracellulare e la specializzazione funzionale degli organelli , 6) Transazioni energetiche : fotosintesi e respirazione cellulare, 7) Controllo della espressione dell’informazione genetica: il braccio afferente del circuito informazionale, 8) La riproduzione delle unità biologiche elementari, 9) Basi cellulari della riproduzione degli organismi

The influence of mesenchyme on the epithelial glycogen and budding activity in mouse embryonic lung developing <i>in vitro</i>

ABSTRACT Experiments have been performed to show the association of epithelial glycogen with budding activity, and their dependence on the nature of the associated mesenchyme. The bronchial mesenchyme associated with the tracheal epithelium induces the appearance of a tracheal bud where glycogen remains present after its removal from the rest of the trachea. The bronchial mesenchyme associated with the tracheal epithelium after the normal disappearance of glycogen, still induces the formation of an epithelial bud where glycogen is clearly demonstrable. The primary left bronchus completely ceases its budding activity when brought in association with metanephrogenic mesenchyme ; glycogen is totally absent from the resting epithelium. The reassociation of the morphogenetically quiescent primary left bronchus with bronchial mesenchyme brings about resumption of budding activity and reappearance of the epithelial glycogen, showing normal bronchial distribution.</jats:p

Relationship of epithelial growth to mitotic rate in mouse embryonic lung developing <i>in vitro</i>

ABSTRACT The rate of cell division was studied as a function of over-all growth of the epithelial tree of the 11-day mouse embryonic lung developing in vitro, under conditions of: (1) normal growth in vitro of intact rudiments; (2) mass reduction; (3) increase of the relative amount of mesenchyme. The over-all rate of epithelial growth under experimental situations (2) and (3) is significantly higher than that of intact rudiments. The epithelial cell proliferation rate is highly correlated with the over-all size of epithelial growth in all cases. It was concluded that the over-all growth and budding activity of the epithelial tree depends on cell division. Reduction in mass and an increased amount of mesenchyme increase the rate of epithelial growth by stimulating the mitotic activity of the epithelial cells.</jats:p

Hydrocortisone-increased glycogen deposition and its dependence on tissue interactions in mouse embryonic lung developing <i>in vitro</i>

ABSTRACT We have performed experiments showing that the epithelial tree of embryonic rudiments, when cultured in vitro in the presence of hydrocortisone, sharply increases its glycogen content. The distribution of the polysaccharide remains very similar to that observed in the absence of the hormone. The increased glycogen deposition in response to the hormonal treatment requires the presence of homologous (bronchial) mesenchyme, as shown by the complete inability of the epithelium to accumulate glycogen when experimentally associated with metanephrogenic mesenchyme. The increased deposition of glycogen in the epithelial tree does not result in an enhanced rate of budding activity.</jats:p