Regulation of hematopoiesis by the BMP signaling pathway in adult zebrafish
Received 26 December 2007; received in revised form 12 August 2008; accepted 21 August 2008. published online 30 October 2008.
Objective
The zebrafish is an established model system for studying the embryonic emergence of tissues and organs, including the hematopoietic system. We hypothesized that key signaling pathways controlling embryonic hematopoiesis continue to be important in the adult, and we sought to develop approaches to test this in zebrafish, focused on the bone morphogenetic protein (BMP) signaling pathway. Functions for this pathway in adult hematopoiesis have been challenging to probe in other models.
Materials and Methods
Several approaches tested the function of BMP signaling during adult zebrafish hematopoiesis. First, we evaluated steady-state hematopoiesis in adult fish that are heterozygous for mutant alleles of Smad5, or are homozygous for mutant alleles, and rescued to adulthood by injection of RNA encoding Smad5. Second, we tested the relative ability of smad5 mutant fish to recover from hemolytic anemia. Third, we generated a transgenic line that targets the expression of a dominant-negative BMP receptor to adult-stage Gata1+ progenitor cells.
Results
Adult fish with a strong mutant smad5 allele are anemic at steady state and, in addition, respond to hemolytic anemia with kinetics that are altered compared to wild-type fish. Fish expressing a mutant BMP receptor in early Gata1+ definitive progenitors generate excessive eosinophils.
Conclusions
Our study provides proof of principle that regulation of adult hematopoiesis can be studied in zebrafish by altering specific pathways. We show that the BMP signaling pathway is relevant for adult hematopoiesis to maintain steady state erythropoiesis, control the erythropoietic response following stress anemia, and to generate normal numbers of eosinophils.
aDepartment of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, USA
bDepartment of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pa., USA
Offprint requests to: Todd Evans, Ph.D., Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Chanin Room 501, Bronx, NY 10461, USA
ABSTRACT