Specification of the primitive myeloid precursor pool requires signaling through Alk8 in zebrafish.
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.
Hogan
Benjamin M
BM
Ludwig Institute for Cancer Research, Post Office Box 2008, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
Layton
Judith E
JE
Pyati
Ujwal J
UJ
Nutt
Stephen L
SL
Hayman
John W
JW
Varma
Sony
S
Heath
Joan K
JK
Kimelman
David
D
Lieschke
Graham J
GJ
D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D019521:Body Patterning; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008954:Models, Biological; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000378:metabolism*; D038042:Myelopoiesis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*; D000099232:Proto-Oncogene Protein Spi-1
D030201:Activin Receptors, Type I; D052004:Bone Morphogenetic Protein Receptors; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D029961:Zebrafish Proteins; D000099232:Proto-Oncogene Protein Spi-1; C498943:Acvr1 protein, mouse; C424203:acvr1l protein, zebrafish