Identification of genes expressed in the migrating primitive myeloid lineage of Xenopus laevis.
BACKGROUND
During primitive hematopoiesis in Xenopus, cebpa and spib expressing myeloid cells emerge from the anterior ventral blood island. Primitive myeloid cells migrate throughout the embryo and are critical for immunity, healing, and development. Although definitive hematopoiesis has been studied extensively, molecular mechanisms leading to the migration of primitive myelocytes remain poorly understood. We hypothesized these cells have specific extracellular matrix modifying and cell motility gene expression.


RESULTS
In situ hybridization screens of transcripts expressed in Xenopus foregut mesendoderm at stage 23 identified seven genes with restricted expression in primitive myeloid cells: destrin; coronin actin binding protein, 1a; formin-like 1; ADAM metallopeptidase domain 28; cathepsin S; tissue inhibitor of metalloproteinase-1; and protein tyrosine phosphatase nonreceptor 6. A detailed in situ hybridization analysis revealed these genes are initially expressed in the aVBI but become dispersed throughout the embryo as the primitive myeloid cells become migratory, similar to known myeloid markers. Morpholino-mediated loss-of-function and mRNA-mediated gain-of-function studies revealed the identified genes are downstream of Spib.a and Cebpa, key transcriptional regulators of the myeloid lineage.


CONCLUSIONS
We have identified genes specifically expressed in migratory primitive myeloid progenitors, providing tools to study how different gene networks operate in these primitive myelocytes during development and immunity.
Perinatal Institute, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.|Division of Neonatology, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.
Zachary N
ZN
Agricola
Perinatal Institute, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.|Division of Neonatology, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.
Amrita K
AK
Jagpal
Perinatal Institute, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.|Division of Neonatology, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.
Andrew W
AW
Allbee
Perinatal Institute, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.|Division of Neonatology, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.
Allison R
AR
Prewitt
Perinatal Institute, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.|Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.
Emily T
ET
Shifley
Perinatal Institute, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.|Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.
Scott A
SA
Rankin
Perinatal Institute, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.|Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.
Aaron M
AM
Zorn
Perinatal Institute, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.|Division of Neonatology, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics College of Medicine, University of Cincinnati, Cincinnati, Ohio.
Alan P
AP
Kenny
D000818:Animals; D019070:Cell Lineage / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics*; D051345:Destrin / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology* / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis / Q000235:genetics*
D051345:Destrin; D008840:Microfilament Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1
ADAM metallopeptidase domain 28 (adam28); CCAAT/enhancer binding protein a(cebpa); Xenopus; actin; destrin (dstn); coronin, actin binding protein 1a (coro1a); cathepsin S (ctss); formin-like 1 (fmnl1); migrating; spib; myeloid; protein tyrosine phosphatase non-receptor 6 (ptpn6); tissue inhibitor of metalloproteinase-1 (timp-1)