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Introduction: The mature 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. Other factors influence the kidney development via regulation of interacting tissues, like vascularization. Mutations in p63, a member of the p53 family of tumor suppression genes, causes Ectrodactylyectodermal dysplasia-clefting syndrome 3, which presents also with genitourinary anomalies. However, Gbx2, a transcription factor mainly known for its role in central nervous system development has not been studied in context with kidney development. Here, we compared the expression of markers of specific nephron segments in kidneys from 18-day embryonic age (E18.5) of p63-/- and Gbx2neo/neo (with 6-10% of WT expression) mice. Research Aim: Gbx2 is not known to be involved in kidney development. However, unusual histology of the kidneys of Gbx2 mutant mice implies otherwise. We aim to identify if and how Gbx2 influences kidney development. Methods: Kidneys from WT, p63-/-, and Gbx2neo/neo mice at E18.5 were embedded in paraffine and serial sectioned (5 mm). The sections 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. Results: The glomerular and tubular structures were similar in in all mice studied. However, HE staining showed excessive red blood cell infiltration in the kidneys of Gbx2neo/neo mice as compared to the kidneys of WT and p63-/- mice. Expression of markers of all nephron segments was significantly less in kidneys from Gbx2neo/ neo mice as compared to kidneys from WT and p63-/- mice. The expression of Na-K ATPase was similar in kidneys from all mice. Discussion: Currently Gbx2 is not linked to kidney development. However, Gbx2 is involved in vascular development. The observed red blood infiltration implies that Gbx2 deficit affects vascular ontogeny during the kidney formation and therefore also affects kidney development and function. Further studies are required and currently underway in our labs to confirm the role of Gbx2 in vascular and kidney development. Significance and implication: This study provides evidence of a yet unknown function of Gbx2 and may help us in understanding the tissue interactions necessary for normal kidney development. Session: Developmental Biology Award Symposium Funding or Support: NSF EiR-HBCU #2000005 (JMZC) 

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.