Global expression analysis of gene regulatory pathways during endocrine pancreatic development.
To define genetic pathways that regulate development of the endocrine pancreas, we generated transcriptional profiles of enriched cells isolated from four biologically significant stages of endocrine pancreas development: endoderm before pancreas specification, early pancreatic progenitor cells, endocrine progenitor cells and adult islets of Langerhans. These analyses implicate new signaling pathways in endocrine pancreas development, and identified sets of known and novel genes that are temporally regulated, as well as genes that spatially define developing endocrine cells from their neighbors. The differential expression of several genes from each time point was verified by RT-PCR and in situ hybridization. Moreover, we present preliminary functional evidence suggesting that one transcription factor encoding gene (Myt1), which was identified in our screen, is expressed in endocrine progenitors and may regulate alpha, beta and delta cell development. In addition to identifying new genes that regulate endocrine cell fate, this global gene expression analysis has uncovered informative biological trends that occur during endocrine differentiation.
Gu
Guoqiang
G
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Wells
James M
JM
Dombkowski
David
D
Preffer
Fred
F
Aronow
Bruce
B
Melton
Douglas A
DA
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins; D005314:Embryonic and Fetal Development / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins; D017403:In Situ Hybridization; D007515:Islets of Langerhans / Q000166:cytology / Q000196:embryology* / Q000254:growth & development; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; C078341:MYT1 protein, human; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases