Specification of the Primitive Myeloid Precursor Pool Requires Signaling through Alk8 in Zebrafish

Abstract

In the zebrafish embryo, primitive hematopoiesis initiates in two spatially distinct regions. Rostrally, the cells of the anterior lateral plate mesoderm (ALPM) give rise exclusively to cells of the myeloid lineage in a pu.1-dependent manner. Caudally, in the posterior lateral plate mesoderm (PLPM), the expression of gata1 defines a precursor pool that gives rise predominantly to the embryonic erythrocytes. The transcription factor scl acts upstream of both gata1 and pu.1 in these precursor pools, activating a series of conserved transcription factors that cell-autonomously specify either myeloid or erythroid fates. However, the mechanisms underlying the spatial separation of the hematopoietic precursor pools and the induction of differential gene expression within these pools are not well understood. We show here that the Bmp receptor lost-a-fin/alk8 is required for rostral pu.1 expression and myelopoiesis, identifying an early genetic event that distinguishes between the induction of anterior and posterior hematopoiesis. Introducing a constitutively active version of the Alk8 receptor led to increased pu.1 expression, but the role of alk8 was independent of the scl-dependent cell-fate pathway. Furthermore, the role of Alk8 in myelopoiesis was genetically separable from its earlier role in dorsal-ventral embryonic patterning.

Genetic control of hematopoietic development in Xenopus and zebrafish

“…5E). Their differentiation potentials indicate that the ALM and PLM are genetically distinct, and it has been demonstrated, for example, that ALK8 signalling is essential for the ALM but dispensable for PLM specification (Hogan et al, 2006). Also, specifi-B C A Walmsley et al, 2002).…”

Live Imaging Reveals Differing Roles of Macrophages and Neutrophils during Zebrafish Tail Fin Regeneration

“…Thus, the larva tail fin regeneration is an ideal system for studying the roles of immune cells in injury-induced tissue regeneration. Moreover, the creations of myeloid lineage-marking transgenic lines (14 -16) and myeloid-defective fish (17) have provided unique opportunities to explore the actions of myeloid leukocytes during epimorphic regeneration in a living organism. However, zebrafish lines in which both macrophage and neutrophil lineages are labeled by fluorescent proteins are still limited.…”

Zebrafish scube1 (Signal Peptide-CUB (Complement Protein C1r/C1s, Uegf, and Bmp1)-EGF (Epidermal Growth Factor) Domain-containing Protein 1) Is Involved in Primitive Hematopoiesis

“…However, recent gain-or lossof-function manipulation of the BMP signal pathway during middle or late gastrulation or even post-gastrulation suggested that BMP signaling also functions in blood fate specification (19,21,(41)(42)(43)(44)(45). Overall, our genetic data suggest that scube1 may regulate the BMP signaling for its later role during somitogenesis in the specification of blood progenitors.…”

“…Morphants-Because human SCUBE1 or SCUBE2 have been implicated in regulating the long range signaling of BMP (3,34) and because BMP signaling is important for mesoderm patterning and specifying the blood fate (19,21,38), we then investigated the genetic relationship between scube1 and bmp genes by co-injection of bmp2b or bmp4 mRNA with scube1 tMO1 in embryos. Overexpression of bmp2b or bmp4 restored scl expression in scube1 morphants (Fig.…”