Fetal lungs of tenascin-C-deficient mice grow well, but branch poorly in organ culture

Roth-Kleiner, Matthias; Hirsch, Emilio; Schittny, Johannes C. (2004). Fetal lungs of tenascin-C-deficient mice grow well, but branch poorly in organ culture. American journal of respiratory cell and molecular biology, 30(3), pp. 360-366. American Lung Association 10.1165/rcmb.2002-0266OC

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Tenascin-C (TNC) is a multidomain extracellular matrix protein that contributes to organogenesis and tumorgenesis. To elucidate its developmental function in the context of TNC deficiency, lung lobes of TNC null mice were obtained at Embryonic Days E11.5 and E12.5 and cultured for 3 d. In lung explants of homozygote TNC-deficient embryos (E12.5) the number of future airway branches was reduced by 36% as compared with wild-type. In heterozygote explants only half of the reduction (18%) was observed. No significant alteration, neither of the explant growth nor of the pattern of airway branching, was noticed in TNC-null explants. However, the terminal endbuds of the transgenic explants were enlarged. The results are supported by a morphologic investigation at Postnatal Day P2, where the airspaces of TNC-deficient lungs appeared larger than in wild-type lungs. Taken together, our results represent the first developmental phenotype of TNC-null mice. We conclude that TNC takes part in the control of fetal lung branching, and that not only the presence of TNC but also its amount is important. Because TNC is predominantly expressed at the growing tip of the future airways, we hypothesize that TNC promotes the penetration into the surrounding mesenchyme and the branching of the growing airways.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Functional Anatomy

UniBE Contributor:

Schittny, Johannes

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

1044-1549

Publisher:

American Lung Association

Language:

English

Submitter:

Johannes Schittny

Date Deposited:

01 Sep 2014 13:53

Last Modified:

07 Dec 2014 10:06

Publisher DOI:

10.1165/rcmb.2002-0266OC

PubMed ID:

12904321

Uncontrolled Keywords:

embryonic E, postnatal P, phosphate-buffered saline PBS, Tenascin-C TNC, transferase-mediated deoxyuridine triphosphate nick end labeling TUNEL

BORIS DOI:

10.7892/boris.50152

URI:

https://boris.unibe.ch/id/eprint/50152

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