Maureen Gannon, Ph.D.
Professor of Medicine, Molecular Physiology and Biophysics, and
Cell and Developmental Biology

 

 


Record History
Added on September 26, 2019 at 12:48 PM by Uttz, Pam
Modified on January 9, 2020 at 2:27 PM by Uttz, Pam
Shared with (contributions)
Public: SPRING Meeting

Meeting Details

Start Date / Time January 15, 2020 at 9:00 AM
End Date / Time January 15, 2020 at 10:00 AM
Duration 1 hour(s)
Location 9455 MRB IV
Presenter Name Maureen Gannon, Ph.D.
Presentation Title Dissecting roles of the Pdx1 C-terminal in pancreas development and beta cell proliferation
Status This meeting has already occurred

Meeting Agenda/Notes

Transcriptional networks are critical to the proper development, differentiation, and expansion of pancreatic islet beta cells, working through enhancers and active promoters that form 3-dimensional hubs. The homeodomain transcription factor Pdx1 is a critical member of the beta cell transcriptional network during embryonic beta cell formation and postnatal life.  Pdx1 is mutated in monogenic forms of human diabetes and plays critical roles in early pancreas specification, organ size and in beta cell formation, proliferation, and identity. Truncation of the C-terminal domain of PDX1 in vivo impacts organ size and leads to a dramatic reduction in the number of endocrine pancreas progenitors in mice.  Notably, mutations in the C-terminus are associated with human type 2 diabetes.  The C-terminus contains several key structural features, including low-glucose-dependent phosphorylation, competitive protein-protein interactions with SPOP/PCIF1 and OC1/HNF6, and a highly intrinsically disordered protein region with unknown function. Interactions with SPOP lead to PDX1 degradation while PDX1 and OC1 cooperate in multipotent progenitor cells to establish the endocrine pancreas gene program. Studies are underway to determine whether the structure and post-translational modification of the PDX1 C-terminus dictates its subcellular localization and interactions with cofactors necessary for pancreatic endocrine differentiation and for proper postnatal growth and function of beta cells.

 

Attachment

Document Spring_2020__Gannon_01.15.pdf - Added on January 9, 2020 at 2:26 PM by Pam Uttz