Neurogenin 3-expressing progenitor cells in the gastrointestinal tract differentiate into both endocrine and non-endocrine cell types.
Mice deficient for the transcription factor neurogenin 3 (ngn3) fail to develop endocrine cells in the intestine and pancreas and show partial endocrine differentiation in the stomach. We expressed Cre recombinase under control of a ngn3 BAC to achieve high fidelity cell lineage tracing in vivo to determine whether endocrine cells in these organs differentiate from NGN3+ precursor cells. Our results indicate that all small intestinal enteroendocrine cells arise from ngn3-expressing cells and confirm that NGN3+ cells give rise to all pancreatic endocrine cells as noted previously. By examining mice at a developmental stage when all of the cell types in the stomach have differentiated, we have delineated region-associated differences in endocrine differentiation. A much smaller fraction of endocrine cells populating the acid-producing region of the stomach is derived from NGN3+ precursor in contrast to the antral-pyloric region. Unexpectedly, ngn3 is expressed in cells that adopt non-endocrine cell fates including significant fractions of goblet and Paneth cells in the intestine and a small number of duct and acinar cells in the pancreas. Rarely, ngn3 was expressed in pluripotent cells in intestinal crypts with resultant labeling of an entire crypt-villus unit. Thus, ngn3 expression occurs in mixed populations of immature cells that are not irreversibly committed to endocrine differentiation.
Schonhoff
Susan E
SE
Division of Gastroenterology, GRASP Digestive Disease Center, Tufts-New England Medical Center, Boston, MA 02111, USA.
Giel-Moloney
Maryann
M
Leiter
Andrew B
AB
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D022202:Chromosomes, Artificial, Bacterial; D017931:DNA Primers; D019858:Enteroendocrine Cells / Q000502:physiology; D041981:Gastrointestinal Tract / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006652:Histological Techniques; D007150:Immunohistochemistry; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice / Q000196:embryology*; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism*; D001616:beta-Galactosidase
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D019426:Integrases; D009419:Nerve Tissue Proteins; D001616:beta-Galactosidase; C407737:Neurog3 protein, mouse; C045073:Cre recombinase