title: The window period of NEUROGENIN3 during human gestation.
abstract: The basic helix-loop-helix transcription factor, NEUROG3, is critical in causing endocrine commitment from a progenitor cell population in the developing pancreas. In human, NEUROG3 has been detected from 8 weeks post-conception (wpc). However, the profile of its production and when it ceases to be detected is unknown. In this study we have defined the profile of NEUROG3 detection in the developing pancreas to give insight into when NEUROG3-dependent endocrine commitment is possible in the human fetus. Immunohistochemistry allowed counting of cells with positively stained nuclei from 7 wpc through to term. mRNA was also isolated from sections of human fetal pancreas and NEUROG3 transcription analyzed by quantitative reverse transcription and polymerase chain reaction. NEUROG3 was detected as expected at 8 wpc. The number of NEUROG3-positive cells increased to peak levels between 10 wpc and 14 wpc. It declined at and after 18 wpc such that it was not detected in human fetal pancreas at 35-41 wpc. Analysis of NEUROG3 transcription corroborated this profile by demonstrating very low levels of transcript at 35-41 wpc, more than 10-fold lower than levels at 12-16 wpc. These data define the appearance, peak and subsequent disappearance of the critical transcription factor, NEUROG3, in human fetal pancreas for the first time. By inference, the window for pancreatic endocrine differentiation via NEUROG3 action opens at 8 wpc and closes between 21 and 35 wpc.
authors.affiliation: Center for Endocrinology and Diabetes; Institute of Human Development; Faculty of Medical & Human Sciences; Manchester Academic Health Sciences Center ; University of Manchester ; Manchester , UK.
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Salisbury
authors.affiliation: Center for Endocrinology and Diabetes; Institute of Human Development; Faculty of Medical & Human Sciences; Manchester Academic Health Sciences Center ; University of Manchester ; Manchester , UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Blaylock
authors.affiliation: Center for Endocrinology and Diabetes; Institute of Human Development; Faculty of Medical & Human Sciences; Manchester Academic Health Sciences Center ; University of Manchester ; Manchester , UK.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Berry
authors.affiliation: Center for Endocrinology and Diabetes; Institute of Human Development; Faculty of Medical & Human Sciences; Manchester Academic Health Sciences Center ; University of Manchester ; Manchester , UK ; Endocrinology Department; Central Manchester University Hospitals NHS Foundation Trust ; Manchester , UK.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Jennings
authors.affiliation: Erasmus MC; University Medical Center ; Rotterdam , The Netherlands ; Department of Pathology; Reinier de Graaf Hospital ; Delft , The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: De Krijger
authors.affiliation: Center for Endocrinology and Diabetes; Institute of Human Development; Faculty of Medical & Human Sciences; Manchester Academic Health Sciences Center ; University of Manchester ; Manchester , UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Piper Hanley
authors.affiliation: Center for Endocrinology and Diabetes; Institute of Human Development; Faculty of Medical & Human Sciences; Manchester Academic Health Sciences Center ; University of Manchester ; Manchester , UK ; Endocrinology Department; Central Manchester University Hospitals NHS Foundation Trust ; Manchester , UK.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Hanley
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D010179:Pancreas / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D011247:Pregnancy; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D012313:RNA; C498695:NEUROG3 protein, human
keywords: NEUROG3, Neurogenin-3; Neurogenin-3 (NEUROG3); SOX9, Sex-determining region Y-box 9; development; dpc, dayspost-conception; endocrine; fetal; human; pancreas; sex-determining region Y-box 9 (SOX9); wpc, weeks post-conception