Role of Gastrulation Brain Homeobox-2 (Gbx2) gene in mouse kidney development

Adult mammalian kidney is derived from the metanephros (nephrons) and mesonephros (collecting system). Several transcription factors such as PAX2, PAX8, CK7, and WT1 are known to regulate the development of kidneys. Mutations in an oncogenic protein p63, a cause of Ectrodactyly-ectodermal dysplasia-clefting syndrome 3, has been shown to cause genitourinary anomalies. However, Gbx2, a transcription factor involved in brain and cardiovascular system maturation has not been studied in context with kidney development. In this study, we compared the expression of markers of specific nephron segments in kidneys from 18-day embryonic age (E18.5) of p63 knock out (KO) and Gbx2 neo/neo (with 6-10% of WT expression) mice. Kidneys from p63 KO or Gbx2 neo/neo mice at E18.5 were embedded in paraffin and sections (5 mm) were studied at a light microscope after staining with Hematoxylin Eosin (HE) and immunohistochemistry. Antibody staining was performed against HNFa (proximal tubule), NKCC2 (loop of Henle), NCC (distal tubule), and Aqp2 (CCT) and Na-K ATPase. HE staining showed excessive red blood cell infiltration in the kidneys of Gbx2 neo/neo mice as compared to the kidneys of p63 KO mice. However, the glomerular and tubular structures were similar in both groups. Expression of markers of all nephron segments was significantly less in kidneys from Gbx2 neo/neo mice as compared to kidneys from p63 KO mice. The expression of Na-K ATPase was similar in kidneys from both mouse groups. Based on our observations, we conclude that Gbx2 may play an important role in kidney development. Gbx2 is not expressed in the kidneys, but its expression is essential for vascular development. Therefore, Gbx2 may play an important role in regulating kidney development through the control of vascular development. Further studies are required to confirm the role of Gbx2 in kidney development. This study provides evidence of an unknown function of Gbx2 and may help us in understanding the mechanisms of kidney development.

R25AG047843

This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.