New genetic kidney atlas will explain kidney disease

An international team of researchers, which included scientists from the University of Queensland, have generated an atlas of genes involved in kidney formation.

This first comprehensive genetic blueprint of a developing mammal organ, will throw light on the genetic and molecular dynamics of kidney formation and help scientists understand how developmental abnormalities occur and how to stop them.

The researchers from the Institute for Molecular Bioscience at The University of Queensland, Harvard University and the Cincinnati Children's Hospital Medical Centre, have created a detailed genome-based atlas which will serve as a resource for understanding healthy and abnormal kidney development and disease.

The atlas shows how the entire genome is regulated to produce thousands of specific genes that are mixed and re-mixed to form genetic teams.

The teams work together to direct formation of 15 embryonic compartments in the developing kidney - from the earliest phases when stem cells are told how to differentiate into specific kidney cells to the development of nephrons, the kidney's primary functioning unit.

Around one in every 500 births results in a kidney development abnormality, so the research provides the start of new insight into genes and genetic programs, critical in determining how kidney stem cells develop into structures in the adult kidney.

Professor Melissa Little, who led the Australian team, says researchers can refer to the atlas to see the gene expression patterns in a normal developing kidney and it will provide a basis of comparison for scientists studying abnormal kidney development, so they can see where gene interactions have gone awry to produce the abnormality.

The researchers created the atlas by analysing mouse embryonic kidneys aged 15.5 days - a developmental time point when multiple stages of kidney formation can be studied at once because of how the organ develops.

The organ's outer layers contain early stem cells that are still differentiating to become specific cell types, while inside the organ, cell-based structures are forming at intermediate and more mature stages and one of the researchers more unexpected discoveries was of new domains of gene expression that marked clusters of cells not previously known to be distinct.

These discoveries came from the careful validation of gene expression in the developing kidney, which was performed using the robotic gene expression analysis platform operating within the Institute for Molecular Bioscience.

The data from the study has been released as an open-access resource for researchers around the world as part of the GenitoUrinary Development Molecular Anatomy Project, a consortium of laboratories funded by the National Institutes of Health to provide research tools for studying the genitourinary tract, including molecular atlases of gene expression in developing organs.

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