Characterization of immune-matched hematopoietic transplantation in zebrafish.

Evaluating hematopoietic stem cell (HSC) function in vivo requires a long-term transplantation assay. Although zebrafish are a powerful model for discovering the genetics of hematopoiesis, hematopoietic transplantation approaches have been underdeveloped. Here we established a long-term reconstitution assay in adult zebrafish.

A non-canonical function of zebrafish telomerase reverse transcriptase is required for developmental hematopoiesis.

Although it is clear that telomerase expression is crucial for the maintenance of telomere homeostasis, there is increasing evidence that the TERT protein can have physiological roles that are independent of this central function. To further examine the role of telomerase during vertebrate development, the zebrafish telomerase reverse transcriptase (zTERT) was functionally characterized. Upon zTERT knockdown, zebrafish embryos show reduced telomerase activity and are viable, but develop pancytopenia resulting from aberrant hematopoiesis.

Transparent adult zebrafish as a tool for in vivo transplantation analysis.

The zebrafish is a useful model for understanding normal and cancer stem cells, but analysis has been limited to embryogenesis due to the opacity of the adult fish. To address this, we have created a transparent adult zebrafish in which we transplanted either hematopoietic stem/progenitor cells or tumor cells. In a hematopoiesis radiation recovery assay, transplantation of GFP-labeled marrow cells allowed for striking in vivo visual assessment of engraftment from 2 hr-5 weeks posttransplant.

Notch and MAML signaling drives Scl-dependent interneuron diversity in the spinal cord.

The ventral spinal cord generates multiple inhibitory and excitatory interneuron subtypes from four cardinal progenitor domains (p0, p1, p2, p3). Here we show that cell-cell interactions mediated by the Notch receptor play a critical evolutionarily conserved role in the generation of excitatory v2aIN and inhibitory v2bIN interneurons. Lineage-tracing experiments show that the v2aIN and v2bIN develop from genetically identical p2 progenitors.

Homing sweet homing: odyssey of hematopoietic stem cells.

The lineage relationship between the blood cells found in the developmentally successive hematopoietic organs has remained elusive. In this issue of Immunity, Murayama et al. (2006) track the migration of nascent hematopoietic stem cells in zebrafish from their site of origin to a newly described intermediate location.

Hematopoietic stem cell fate is established by the Notch-Runx pathway.

Identifying the molecular pathways regulating hematopoietic stem cell (HSC) specification, self-renewal, and expansion remains a fundamental goal of both basic and clinical biology. Here, we analyzed the effects of Notch signaling on HSC number during zebrafish development and adulthood, defining a critical pathway for stem cell specification. The Notch signaling mutant mind bomb displays normal embryonic hematopoiesis but fails to specify adult HSCs.

Isolation and characterization of runxa and runxb, zebrafish members of the runt family of transcriptional regulators.

Objective: The AML/RUNX family of transcription factors plays important roles in hematopoiesis, neurogenesis, bone development, and segmentation in vertebrate embryos. The aim of this study was to isolate runt-related genes in a genetically and embryologically exploitable system, the zebrafish, and characterize their function during hematopoietic development.

Materials And Methods: Two runt-related genes were isolated by degenerate PCR and standard library screening, and a radiation hybrid panel, T51 RH, was used to resolve their chromosomal localization.

Portrait of a stem cell.

There is great enthusiasm for the potential use of stem cells in treating tissue degenerative disorders, but little is known about the intrinsic molecular programs defining self-renewal and differentiation. New data sets produced by transcriptional profiling of purified stem cell populations begin to establish the nature of "stemness."