Fate mapping of ptf1a-expressing cells during pancreatic organogenesis and regeneration in zebrafish

Background: Pancreas development in zebrafish shares many features with mammals, including the participation of epithelial progenitor cells expressing pancreas transcription factor 1a (ptf1a). However, to date it has remained unclear whether, as in mammals, ptf1a-expressing zebrafish pancreatic progenitors are able to contribute to multiple exocrine and endocrine lineages. To delineate the lineage potential of ptf1a-expressing cells, we generated ptf1a:creER^T2 transgenic fish and performed genetic-inducible lineage tracing in developmental, regenerating, and ptf1a-deficient zebrafish pancreas. Results: In addition to their contribution to the acinar cell lineage, ptf1a-expressing cells give rise to both pancreatic Notch-responsive-cells (PNCs) as well as small numbers of endocrine cells during pancreatic development. In fish with ptf1a haploinsufficiency, a higher proportion of ptf1a lineage-labeled cells are traced into the PNC and endocrine compartments. Further reduction of ptf1a gene dosage converts pancreatic progenitor cells to gall bladder and other non-pancreatic cell fates. Conclusions: Our results confirm the presence of multipotent ptf1a-expressing progenitor cells in developing zebrafish pancreas, with reduced ptf1a dosage promoting greater contributions towards non-acinar lineages. As in mammals, loss of ptf1a results in conversion of nascent pancreatic progenitor cells to non-pancreatic cell fates, underscoring the central role of ptf1a in foregut tissue specification.