Functional domains of the FgfrL1 receptor.

Gerber, Simon D; Beauchamp, Philippe; Zhuang, Lei; Villiger, Peter M.; Trueb, Beat (2020). Functional domains of the FgfrL1 receptor. Developmental biology, 461(1), pp. 43-54. Elsevier 10.1016/j.ydbio.2020.01.003

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FgfrL1 is a novel growth factor receptor that is primarily expressed in musculoskeletal tissues and the kidney. FgfrL1-deficient mice have a malformed diaphragm and no kidneys. Such animals die immediately after birth because they are not able to inflate their lungs. The FgfrL1 molecule is composed of three extracellular Ig domains, a transmembrane helix and a short intracellular domain. To investigate the contribution of each of these domains to the function of the novel receptor, we generated mice with deletions of the individual domains. Mice lacking the intracellular domain are viable and phenotypically normal. Mice lacking the first (N-terminal) Ig domain are also viable and normal, but have a reduced life span. Mice lacking the Ig2 or the Ig3 domain are born alive, but die within 24 ​h after birth. Ig2-deficient animals exhibit substantially smaller kidneys than wild-type littermates and contain a lower number of glomeruli. Ig3-deficient mice completely lack metanephric kidneys. Interestingly, both the Ig2 and the Ig3-deficient animals show only minor alterations in the diaphragm, which still enables them to inflate their lungs after birth. Our results demonstrate that the principal function of the FgfrL1 receptor is to control the growth of the metanephric kidneys by regulating nephrogenesis. It appears that this function is primarily accomplished by the Ig3 domain with some contribution of the Ig2 domain. It is conceivable that the two domains interact with an Fgf ligand and another molecule from the surface of neighboring cells to induce condensation of the metanephric mesenchyme to renal epithelia and glomeruli.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology

UniBE Contributor:

Zhuang, Lei; Villiger, Peter and Trueb, Beat

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0012-1606

Publisher:

Elsevier

Language:

English

Submitter:

Marlise Bühler Zimmermann

Date Deposited:

23 Dec 2020 15:45

Last Modified:

23 Dec 2020 15:45

Publisher DOI:

10.1016/j.ydbio.2020.01.003

PubMed ID:

31923383

Uncontrolled Keywords:

Fibroblast growth factor receptor Kidney development Mesenchymal-to-epithelial transition (MET) Nephrogenesis Renal vesicle Transgenic mice

BORIS DOI:

10.48350/149773

URI:

https://boris.unibe.ch/id/eprint/149773

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