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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.
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From Development to Function: Hands-On & Inexpensive Clay Modeling of Mammalian Kidney Development
In light of the coronavirus disease 2019 (COVID-19), recent clinical research has demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects breathing and internal organs, especially the kidneys and liver function. It is evident that the kidneys are induced by the virus through the course of the medication treatments, such as the side effects that lead to kidney and liver damage. In order to scaffold kidney pathophysiology with normal kidney development and function in a virtual class or lab setting during the COVID-19 pandemic, we have developed a hands-on and cost-effective clay modeling teaching tool at the undergraduate level for learning about kidney anatomy and development. Given remote teaching, this innovative tool can be used to link the structure to molecular and cellular function through an easy hands-on model for both learning and teaching demonstration for all students.
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- Award ID(s):
- 1852032
- PAR ID:
- 10630049
- Publisher / Repository:
- University of California Press
- Date Published:
- Journal Name:
- The American Biology Teacher
- Volume:
- 84
- Issue:
- 3
- ISSN:
- 0002-7685
- Page Range / eLocation ID:
- 172 to 175
- Subject(s) / Keyword(s):
- kidney development inexpensive clay modeling toolkit kidney function SARS-CoV-2 COVID-19 kidney injury and repair
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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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)more » « less
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null (Ed.)Abstract This review summarizes published findings of the beneficial and harmful effects on the heart, lungs, immune system, kidney, liver, and central nervous system of 47 drugs that have been proposed to treat COVID-19. Many of the repurposed drugs were chosen for their benefits to the pulmonary system, as well as immunosuppressive and anti-inflammatory effects. However, these drugs have mixed effects on the heart, liver, kidney, and central nervous system. Drug treatments are critical in the fight against COVID-19, along with vaccines and public health protocols. Drug treatments are particularly needed as variants of the SARS-Cov-2 virus emerge with some mutations that could diminish the efficacy of the vaccines. Patients with comorbidities are more likely to require hospitalization and greater interventions. The combination of treating severe COVID-19 symptoms in the presence of comorbidities underscores the importance of understanding the effects of potential COVID-19 treatments on other organs.more » « less
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Kidney exchange, where candidates with organ failure trade incompatible but willing donors, is a life-saving alternative to the deceased donor waitlist, which has inadequate supply to meet demand. While fielded kidney exchanges see huge benefit from altruistic kidney donors (who give an organ without a paired needy candidate), a significantly higher medical risk to the donor deters similar altruism with livers. In this paper, we begin by exploring the idea of large-scale liver exchange, and show on demographically accurate data that vetted kidney exchange algorithms can be adapted to clear such an exchange at the nationwide level. We then propose cross-organ donation where kidneys and livers can be bartered for each other. We show theoretically that this multi-organ exchange provides linearly more transplants than running separate kidney and liver exchanges. This linear gain is a product of altruistic kidney donors creating chains that thread through the liver pool; it exists even when only a small but constant portion of the donors on the kidney side of the pool are willing to donate a liver lobe. We support this result experimentally on demographically accurate multi-organ exchanges. We conclude with thoughts regarding the fielding of a nationwide liver or joint liver-kidney exchange from a legal and computational point of view.more » « less
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1525/abt.2022.84.3.172
