Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient mice.
In most mammals the pancreas develops from the foregut endoderm as ventral and dorsal buds. These buds fuse and develop into a complex organ composed of endocrine, exocrine and ductal components. This developmental process depends upon an integrated network of transcription factors. Gene targeting experiments have revealed critical roles for Pdx1, Isl1, Pax4, Pax6 and Nkx2-2 (refs 3,4,5,6,7, 8,9,10). The homeobox gene HLXB9 (encoding HB9) is prominently expressed in adult human pancreas, although its role in pancreas development and function is unknown. To facilitate its study, we isolated the mouse HLXB9 orthologue, Hlxb9. During mouse development, the dorsal and ventral pancreatic buds and mature beta-cells in the islets of Langerhans express Hlxb9. In mice homologous for a null mutation of Hlxb9, the dorsal lobe of the pancreas fails to develop. The remnant Hlxb9-/- pancreas has small islets of Langerhans with reduced numbers of insulin-producing beta-cells. Hlxb9-/- beta-cells express low levels of the glucose transporter Glut2 and homeodomain factor Nkx 6-1. Thus, Hlxb9 is key to normal pancreas development and function.
Harrison
K A
KA
Laboratory of Immunoregulation National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Thaler
J
J
Pfaff
S L
SL
Gu
H
H
Kehrl
J H
JH
D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D005136:Eye Proteins; D051858:Forkhead Transcription Factors; D005838:Genotype; D005934:Glucagon / Q000378:metabolism; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D010179:Pancreas / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism; D010191:Pancreatic Polypeptide / Q000378:metabolism; D012097:Repressor Proteins; D013004:Somatostatin / Q000378:metabolism; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins
D004268:DNA-Binding Proteins; D005136:Eye Proteins; C477894:FOXI1 protein, human; C106349:FOXJ1 protein, human; D051858:Forkhead Transcription Factors; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D007328:Insulin; D060850:LIM-Homeodomain Proteins; C490003:MNX1 protein, human; C000715631:NKX2-2 protein, human; D009419:Nerve Tissue Proteins; C000715627:Nkx2-2 protein, mouse; D009687:Nuclear Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; C063843:insulin gene enhancer binding protein Isl-1; C000715630:nkx2.2b protein, zebrafish; C084010:pancreatic and duodenal homeobox 1 protein; C084059:Hb9 protein, mouse; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D005934:Glucagon