DevelopmentalBiology@NIH::Faculty:PI:Anton Jetten Ph.D

Principal Investigators (PI)

Anton Jetten Ph.D

Senior Investigator

Deputy Chief of Immunity,
Inflammation and Disease/Cell Biology

111 T.W. Alexander Drive,
Bldg. 101, Rm.D264
Research Triangle Park, NC 27709

Office: (984) 287-4094

Email: jetten@niehs.nih.gov

IRP page

IC: NIEHS

Anton Jetten obtained his Ph.D. in Microbiology from the University of Nijmegen, The Netherlands. He did his postdoctoral research at MIT before moving to the Roche Institute of Molecular Biology and the NCI where he studied the mechanism of action and functions of retinoic acid. In 1982, he was appointed as Principal Investigator at NIEHS, where he became Lab. Chief for ten years and currently functions as Deputy Chief of IIDL. At NIEHS, his research has been focusing on the mechanism of action and physiological functions of two families of transcription factors, the retinoic acid-related orphan receptor gamma (ROR ) and GLI-Similar 1-3 (GLIS1-3), genes that were discovered by his group including their roles in development and disease.

Link to Pubmed

Jeon K, Kumar D, Conway AE, Park K, Jothi R, Jetten AM. (2019) GLIS3 transcriptionally activates WNT genes to direct differentiation of human embryonic stem cells to posterior neural progenitors. Stem Cells37(2):202-215. doi: 10.1002/stem.2941.
Kang HS, Kumar D, Liao G, Lichti-Kaiser K, Gerrish K, Liao XH, Refetoff S, Jothi R, Jetten AM. (2017) GLIS3 is indispensable for TSH/TSHR-dependent thyroid hormone biosynthesis and follicular cell proliferation. J. Clin. Invest.127(12):4326-4337. doi: 10.1172/JCI94417.
Kang HS, Chen LY, Lichti-Kaiser K, Liao G, Gerrish K, Bortner CD, Yao HH, Eddy EM, Jetten AM. (2016) Transcription factor Glis3: a new and critical regulator of postnatal stages of mouse spermatogenesis Stem Cells34(11):2772-2783. doi: 10.1002/stem.2449
Kang HS, Takeda Y, Jeon K, Jetten AM. (2016) The spatiotemporal pattern of Glis3 expression indicates a regulatory function in bipotent and endocrine progenitors during early pancreatic development and in beta, PP and ductal cells. PLOS ONe11(6):e0157138. doi: 10.1371/journal.pone.0157138.
Donald N. Cook, Hong Soon Kang, and Anton M. Jetten (2015) Retinoic acid-related Orphan Receptors (RORs): Regulatory functions in immunity, development, circadian rhythm, and metabolism. Nucl. Receptor Res.2: 101185. doi: 10.11131/2015/101185

Currently there are no job openings.

Research has been focusing on the mechanism of action and physiological functions of two families of transcription factors, ROR and GLIS1-3. ROR was shown to play a critical role in several in several immune cells, including the generation of Th17 cells and lymph node development, and in the regulation of lipid and glucose metabolism. GLIS3 is essential for the generation of pancreatic beta cells and spermatogenesis, and is essential for thyroid hormone biosynthesis and maintenance of normal renal functions. Deficiency in GLIS3 in humans and mice results to impaired beta cell generation and diabetes, hypothyroidism, polycystic kidney disease, and infertility. RNA-Seq and ChIP-Seq analysis demonstrated that a number of genes that are critical for these biological processes are directly regulated by GLIS3. In addition, GLIS3 is able to direct the differentiation of human embryonic stem cells along the posterior neural progenitor lineage by directly regulating the transcription of the strong posteriorizing factor, WNT3A, instead of the default anterior lineage.

The group consists of 5 postdoctoral fellows and one Staff fellow. We have weekly group meetings to discuss the reserach projects. Postdocs present poster or talks at NIEHS Science day, Genomics Day and Lab retreats as well as scientific meetings and participate in Career Day.

GLIS3 is essential for thyroid hormone biosynthesis. A. GLIS3 expression is restricted to thyroid follicular cells where it directly regulates the transcription of several genes required for thyroid hormone biosynthesis, particularly the two iodide transporter genes, NIS and PDS. Loss of GLIS3 causes a dramatic decrease in NIS and PDS expression and iodide transport, and consequently reduced thyroid hormone biosynthesis and hypothyroidism. B. Low iodide diet (LID) greatly elevates blood TSH levels. Interaction of TSH with the TSHR in thyroid follicular cells activates several kinase pathways and expression of the thyroid biosynthetic genes, including NIS and PDS, and cell cycle genes. However, these genes are not induced by TSH in GLIS3-deficient thyroid follicular cells suggesting that GLIS3 mediates the downstream effects of TSH/TSHR.

Schematic of the multiple functions of GLIS3 in the pancreas. GLIS3 protein is first detectable in bipotent cells (BPCs) and is not expressed in multipotent progenitor cells (MPCs) or acinar cells. GLIS3 protein remains expressed in preductal and ductal cells and in endocrine progenitors. When the endocrine progenitors differentiate into the five endocrine cell types, it remains expressed in  and PP cells, but is repressed in , , and ∂ cells. GLIS3 deficiency inhibits differentiation of BPCs into NGN3+ endocrine progenitors and as a consequence the generation of endocrine cells. In addition, loss of GLIS3 function inhibits  cell maturation and greatly reduces insulin gene expression. GLIS3 deficiency also causes dilation of the pancreatic ducts and repression of Ppy expression in PP cells.

GLIS3 is required for early postnatal spermatogenesis. At PND1, non-mitotic gonocytes differentiate into spermatogonial stem cells (SSCs), which give rise to several spermatogonial progenitor (SPCs) subpopulations (As, Apr, Aal) with decreasing self-renewal capacity. These cells subsequently give rise to c-KIT+ differentiated spermatogonia and eventually mature spermatozoa. GLIS3 expression is restricted to gonocytes, SSCs, and SPCs. Loss of GLIS3 expression affects self-renewal of SSCs and early differentiation and impairs the generation of c-KIT+ differentiated spermatogonia leading to infertility.

Proposed model for GLIS3-mediated shift in neural progenitor cell lineage specification