Kidney Week

Abstract: FR-PO927

Genetic Regulation of Intermediate Mesoderm Specification

Session Information

• Development, Stem Cells, Regenerative Medicine - II
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 501 Development, Stem Cells, and Regenerative Medicine: Basic

Authors

• Perens, Elliot, University of California, San Diego, La Jolla, California, United States

Elliot Perens,

• Hernandez, Jasmine, University of California, San Diego, La Jolla, California, United States

Jasmine Hernandez,

• Houk, Andrew, University of California, San Diego, La Jolla, California, United States

Andrew Houk,

• Garske, Kristina M., University of California, Los Angeles, Los Angeles, California, United States

Kristina M. Garske,

• Teng, Camilla, University of Southern California, Los Angeles, California, United States

Camilla Teng,

• Crump, Gage, University of Southern California, Los Angeles, California, United States

Gage Crump,

• Yelon, Deborah, University of California, San Diego, La Jolla, California, United States

Deborah Yelon,

Background

The kidneys are derived from the intermediate mesoderm (IM), yet the pathways that determine the precise dimensions of the IM in the early embryo are poorly understood. We have found that the bHLH transcription factor Hand2 limits the size of the pronephron by refining IM dimensions. In hand2 mutants, the IM is expanded, and the IM is diminished when hand2 is overexpressed. The hand2-expressing portion of the posterior mesoderm lies laterally adjacent to the IM, and a set of venous precursors arises at the interface between these two territories. hand2 promotes venous precursor development while suppressing IM formation in this region. Furthermore, Hand2 and the similarly localized zinc-finger transcription factor Osr1 have functionally antagonistic influences on both kidney and vein development.

Methods

Our studies of hand2 and osr1 provide valuable entry points for the identification of additional factors that regulate IM specification. How do hand2 and osr1 coordinate the development of the IM and venous progenitor populations? Do hand2 and osr1 impact the same genes as they execute these functions? To address these questions, we aim to identify additional genes in the hand2 and osr1 pathways.

Results

Preliminary analysis has revealed a potent role for bHLH transcription factor Twist1a in modulating IM and vessel precursor formation. Furthermore, to identify genes regulated by hand2, we have evaluated expression profiles from wild-type, hand2 loss-of-function, and hand2 gain-of-function embryos. Additionally, to increase the sensitivity of our investigation, we have compiled expression profiles from sorted hand2-expressing cells in wild-type and hand2 loss-of-function embryos. We are currently analyzing our most intriguing candidate genes, including twist1a, through loss-of-function, gain-of-function, and genetic epistasis experiments to determine their roles in IM formation and their genetic interaction with hand2 and osr1; updated findings will be presented.

Conclusion

Together, our studies will elucidate the roles of hand2 and osr1 in defining the boundaries of the IM by balancing formation of the kidney and vein lineages.

Funding

• NIDDK Support