David B. Wilson, M.D., Ph.D.

Developmental Biology

Developmental, Regenerative and Stem Cell Biology Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-286-2834

  • 314-286-2791

  • 314-286-2892

  • 3102 McDonnell Pediatric Research Building

  • wilson_d@wustl.edu

  • http://peds.wustl.edu/faculty/Wilson_David_B/

  • embryonic development, lung development, mouse models, transcriptional regulation

  • Role of transcription factors in differentiation and development

Research Abstract:

Our work centers on GATA binding proteins, a group of zinc finger transcription factors implicated in lineage commitment. Two members of this family, GATA4 and GATA6, are preferentially expressed in heart, endoderm derivatives, gonadal somatic cells, and mesenchymal cells of the fetal diaphragm and lung. Using gene targeting, we have shown that GATA4 expression in extraembryonic endoderm is essential for ventral morphogenesis in the mouse and that expression of this factor in foregut endoderm is required for proper differentiation of gastric epithelium. More recently we have found that Gata4 haploinsufficient mice are predisposed to congenital diaphragmatic hernias and primary lung defects.

Another area of interest is the role of GATA factors in the regulation of steroidogenic cell differentiation. Our experimental system takes advantage of the observation that GATA-4 normally is expressed in gonadal but not adrenocortical steroidogenic cells of the adult mouse. Interestingly, certain inbred strains of mice develop sex steroid-producing adrenocortical neoplasms in response to prepubertal gonadectomy. This phenomenon is thought to reflect metaplasia of competent cells in the adrenal gland, which transform into gonadal-like stroma in response to changes in the hormonal milieu, and increased expression of GATA4 is a hallmark of this transformation. To examine the signaling pathways involved in this form of tissue-type switching, we have created new inbred and transgenic models of adrenocortical neoplasia .

Selected Publications:

Röhrig T, Pihlajoki M, Ziegler R, Cochran RS, Schrade A, Schillebeeckx M, Mitra RD, Heikinheimo M, Wilson
DB. (2015) Toying with fate: Redirecting the differentiation of adrenocortical progenitor cells into gonadal-like tissue. Mol Cell Endocrinol. 408:165-177. PMCID: PMC4417465

Schillebeeckx M, Pihlajoki M, Gretzinger E, Yang W, Thol F, Hiller T, Löbs AK, Röhrig T, Schrade A, Cochran R, Jay PY, Heikinheimo M, Mitra RD, Wilson DB. (2015) Novel markers of gonadectomy-induced adrenocortical neoplasia in the mouse and ferret. Mol Cell Endocrinol. 399:122-30. PMCID: PMC4262703

Pihlajoki M, Gretzinger E, Cochran R, Kyrönlahti A, Schrade A, Hiller T, Sullivan L, Shoykhet M, Schoeller EL,Brooks MD, Heikinheimo M, Wilson DB. (2013) Conditional mutagenesis of Gata6 in SF1-positive cells causesgonadal-like differentiation in the adrenal cortex of mice. Endocrinology. 154(5):1754-67. PMCID: PMC3628026

Krachulec J, Vetter M, Schrade A, Löbs AK, Bielinska M, Cochran R, Kyrönlahti A, Pihlajoki M, Parviainen H,
Jay PY, Heikinheimo M, Wilson DB. (2012) GATA4 is a critical regulator of gonadectomy-induced adrenocortical tumorigenesis in mice. Endocrinology. 153(6):2599-611. PMCID:PMC3359595

Wilson MP, Hugge C, Bielinska M, Nicholas P, Majerus PW, Wilson DB. (2009). Neural tube defects in mice withreduced levels of inositol 1,3,4-trisphosphate 5/6-kinase. Proc Natl Acad Sci U S A. 106(24):9831-5. PMCID: PMC2701051

Jay PY, Bielinska M, Erlich JM, Mannisto S, Pu WT, Heikinheimo M, Wilson DB. (2007). Impaired mesenchymal cellfunction in Gata4 mutant mice leads to diaphragmatic hernias and primary lung defects. Dev Biol. 301(2):602-14. PMCID: PMC1808541

Last Updated: 8/29/2016 11:56:51 AM

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