The LIM‐homeodomain transcription factor LMX1B supports the maintenance of differentiated podocytes by modulating the actin cytoskeleton

Abstract

Mutations in the LMX1B gene cause a rare autosomal‐dominant disorder affecting the development of the limbs, eyes, brain and kidneys, called nail‐patella syndrome. In order to determine the role of LMX1B in the differentiation and maintenance of the renal filtration barrier we generated inducible podocyte‐specific Lmx1b knockout mice. Already one week after inactivation of Lmx1b in adult mice foot process effacement and rising proteinuria were detectable underlining the physiological significance of LMX1B in the maintenance of differentiated podocytes.Using a variety of different biophysical assays such as electric cell‐substrate impedance sensing, nano‐scale particle tracking, magnetic tweezer measurements and adhesion assays we were able to demonstrate that LMX1B affects the organization of the actin cytoskeleton. These findings were corroborated by micro array data which reveal LMX1B‐regulated genes encoding actin cytoskeleton‐associated proteins. Our data highlights the importance of LMX1B in fully differentiated podocytes and describes an essential role of LMX1B for the maintenance of an appropriately structured actin cytoskeleton in podocytes. This work was supported by the German Research Council through SFB 699.