Abstract

Lmx1b is a transcription factor necessary for kidney development. In humans, haploinsufficiency causes Nail Patella Syndrome frequently with chronic renal failure. In Lmx1b knockout mice, glomerular basement membrane formation is impaired, blocking filtration, urine production and long term survival. The mechanisms used by Lmx1b to direct basement membrane formation remain unclear. Recent microarray studies in the limb have implicated the proteoglycans Keratocan, Lumican, and Decorin (KLD) as downstream targets of Lmx1b. We hypothesized that Lmx1b might also regulate the KLD proteoglycans during kidney development.To determine the role of Lmx1b in regulating the KLD proteoglycans, we compared the expression patterns of Lmx1b, Podocin, Keratocan, Lumican, and Decorin in the developing chicken kidney using whole mount in situ hybridization.We found that Keratocan expression localized to nephric tubules and collecting ducts, Lumican expression was associated with nephric tubules, and Decorin expression surrounded Bowman's capsules and nephric tubules. Correspondingly, Lmx1b is expressed in Bowman's capsule and in nephric tubules. Thus, the expression of Decorin complements the expression of Lmx1b.Our data suggests Decorin is a target of Lmx1b regulation during nephrogenesis. Further research is needed to determine the functional role of KLD proteoglycans in kidney development.Grant Funding Source: Departmental

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