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Jeffrey A. Whitsett, MDProfessorCo-Director, Perinatal InstituteDepartment of Pediatrics; Chief, Section of Neonatology, Perinatal and Pulmonary BiologyVisit the Whitsett Lab Site
Dr. Whitsett’s digestive disease related project focuses on the role of Sox, KLF, and Ets protein in GI development and function. His work has led him to identify genes and processes critical for gastrointestinal development. For example SPDEF is an ETS transcription factor that has been shown to play a role in mucous cell differentiation in the lung. Together with Dr. Shroyer, Dr. Whitsett has discovered that SPDEF controls intestinal mucous (goblet) cell maturation and cell cycle exit. Additionally, Dr. Whitsett is examining the role of the Kruppel family transcription factor Klf5 in embryonic intestinal development with Dr. Shroyer.
Recently, Dr. Whitsett along with his colleague Dr. Wells established that the extrahepatobiliary system shares a common origin with the ventral pancreas and not the liver. These pancreatobiliary progenitor cells coexpress the transcription factors PDX1 and SOX17 at E8.5 and their segregation into a PDX1+ ventral pancreas and a SOX17+ biliary primordium is Sox17-dependent. Furthermore, they were able to demonstrate that deleting Sox17 at E8.5 resulted in the loss of biliary structures and ectopic pancreatic tissue in the liver bud and common duct. However when they overexpressed Sox17 development of the pancreas was suppressed and there was evidence of ectopic biliary-like tissue throughout the PDX1+ domain.
Dr. Whitsett collaborates with Drs. Wells and Zorn on KLF-5 and Sox proteins in GI-gall bladder-pancreas specification. Additionally, he works with Dr. Shroyer examining GI goblet cell differentiation.
Click image to enlarge
Immunofluorescence for BrdU (green), Spdef (red), and DAPI (blue) is shown for Spdef dox-intestine (B) and Spdef WT (A) mice treated with doxycycline for 2 days. Crypts that express Spdef are outlined in (B) by the red line. (C) Quantitation of BrdU-labeled crypt cells from Spdef WT mice (white bars) and from Spdef-expressing crypts in Spdef dox-intestine mice (black bars) showed less proliferation of Spdef-expressing crypts in both colon and ileum. Figure from Exp Cell Res 2010;316:452-65.
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