Sustained Neurog3 expression in hormone-expressing islet cells is required for endocrine maturation and function.
Neurog3 (Neurogenin 3 or Ngn3) is both necessary and sufficient to induce endocrine islet cell differentiation from embryonic pancreatic progenitors. Since robust Neurog3 expression has not been detected in hormone-expressing cells, Neurog3 is used as an endocrine progenitor marker and regarded as dispensable for the function of differentiated islet cells. Here we used 3 independent lines of Neurog3 knock-in reporter mice and mRNA/protein-based assays to examine Neurog3 expression in hormone-expressing islet cells. Neurog3 mRNA and protein are detected in hormone-producing cells at both embryonic and adult stages. Significantly, inactivating Neurog3 in insulin-expressing beta cells at embryonic stages or in Pdx1-expressing islet cells in adults impairs endocrine function, a phenotype that is accompanied by reduced expression of several Neurog3 target genes that are essential for islet cell differentiation, maturation, and function. These findings demonstrate that Neurog3 is required not only for initiating endocrine cell differentiation, but also for promoting islet cell maturation and maintaining islet function.
Wang
Sui
S
Program in Developmental Biology and Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Jensen
Jan N
JN
Seymour
Philip A
PA
Hsu
Wei
W
Dor
Yuval
Y
Sander
Maike
M
Magnuson
Mark A
MA
Serup
Palle
P
Gu
Guoqiang
G
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D055879:Gene Knock-In Techniques; D005951:Glucose Tolerance Test; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D051792:Basic Helix-Loop-Helix Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C407737:Neurog3 protein, mouse