title: Differential requirement for ptf1a in endocrine and exocrine lineages of developing zebrafish pancreas.
abstract: Mammalian studies have implicated important roles for the basic helix-loop-helix transcription factor Ptf1a-p48 in the development of both exocrine and endocrine pancreas. We have cloned the Ptf1a-p48 ortholog in Danio rerio. Early zebrafish ptf1a expression is observed in developing hindbrain and in endodermal pancreatic precursors. Analysis of ptf1a and insulin expression reveals a population of exocrine precursors that, throughout early development, are temporally and spatially segregated from endocrine elements. Morpholino-mediated knockdown of ptf1a confirms early divergence of these endocrine and exocrine lineages. Ptf1a morphants lack differentiated exocrine pancreas, but maintain normal differentiation and organization of the principal islet. In addition to the exocrine phenotype, ptf1a knockdown also reduces the prevalence of a small population of anterior endocrine cells normally found outside the principal islet. Together, these findings suggest the presence of distinct ptf1a-dependent and ptf1a-independent precursor populations in developing zebrafish pancreas.
authors.affiliation: Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Lin
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Biankin
authors.forename: Marko E
authors.initials: ME
authors.lastname: Horb
authors.forename: Bidyut
authors.initials: B
authors.lastname: Ghosh
authors.forename: Nijaguna B
authors.initials: NB
authors.lastname: Prasad
authors.forename: Nelson S
authors.initials: NS
authors.lastname: Yee
authors.forename: Michael A
authors.initials: MA
authors.lastname: Pack
authors.forename: Steven D
authors.initials: SD
authors.lastname: Leach
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage / Q000502:physiology; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D006652:Histological Techniques; D018398:Homeodomain Proteins; D017403:In Situ Hybridization; D007328:Insulin / Q000378:metabolism; D008969:Molecular Sequence Data; D009024:Morphogenesis; D010179:Pancreas / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D007328:Insulin; D015534:Trans-Activators; D014157:Transcription Factors; C084010:pancreatic and duodenal homeobox 1 protein; C062602:transcription factor PTF1