Identification of molecular compartments and genetic circuitry in the developing mammalian kidney

Author:

Yu Jing12,Valerius M. Todd1,Duah Mary1,Staser Karl1,Hansard Jennifer K.1,Guo Jin-jin1,McMahon Jill1,Vaughan Joe1,Faria Diane1,Georgas Kylie3,Rumballe Bree3,Ren Qun2,Krautzberger A. Michaela1,Junker Jan P.4,Thiagarajan Rathi D.3,Machanick Philip3,Gray Paul A.5,van Oudenaarden Alexander4,Rowitch David H.6,Stiles Charles D.7,Ma Qiufu5,Grimmond Sean M.3,Bailey Timothy L.3,Little Melissa H.3,McMahon Andrew P.1

Affiliation:

1. Department of Stem Cell and Regenerative Biology, Department of Molecular and Cellular Biology, Harvard Stem Cell Institute, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.

2. Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

3. Institute for Molecular Bioscience, University of Queensland, St Lucia 4072, Australia.

4. Department of Physics and Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.

5. Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.

6. Departments of Pediatrics and Neurological Surgery, Howard Hughes Medical Institute, University of California San Francisco, 35 Medical Center Way, San Francisco, CA 94143, USA.

7. Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.

Abstract

Lengthy developmental programs generate cell diversity within an organotypic framework, enabling the later physiological actions of each organ system. Cell identity, cell diversity and cell function are determined by cell type-specific transcriptional programs; consequently, transcriptional regulatory factors are useful markers of emerging cellular complexity, and their expression patterns provide insights into the regulatory mechanisms at play. We performed a comprehensive genome-scale in situ expression screen of 921 transcriptional regulators in the developing mammalian urogenital system. Focusing on the kidney, analysis of regional-specific expression patterns identified novel markers and cell types associated with development and patterning of the urinary system. Furthermore, promoter analysis of synexpressed genes predicts transcriptional control mechanisms that regulate cell differentiation. The annotated informational resource (www.gudmap.org) will facilitate functional analysis of the mammalian kidney and provides useful information for the generation of novel genetic tools to manipulate emerging cell populations.

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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