title: Zebrafish numb and numblike are involved in primitive erythrocyte differentiation.
abstract: BACKGROUND
  Notch signaling is an evolutionarily conserved regulatory circuitry implicated in cell fate determination in various developmental processes including hematopoietic stem cell self-renewal and differentiation of blood lineages. Known endogenous inhibitors of Notch activity are Numb-Nb and Numblike-Nbl, which play partially redundant functions in specifying and maintaining neuronal differentiation. Nb and Nbl are expressed in most tissues including embryonic and adult hematopoietic tissues in mice and humans, suggesting possible roles for these proteins in hematopoiesis.
  
  
  RESULTS
  We employed zebrafish to investigate the possible functional role of Numb and Numblike during hematopoiesis, as this system allows a detailed analysis even in embryos with severe defects that would be lethal in other organisms. Here we describe that nb/nbl knockdown results in severe reduction or absence of embryonic erythrocytes in zebrafish. Interestingly, nb/nbl knocked-down embryos present severe downregulation of the erythroid transcription factor gata1. This results in erythroblasts which fail to mature and undergo apoptosis. Our results indicate that Notch activity is increased in embryos injected with nb/nbl morpholino, and we show that inhibition of Notch activation can partially rescue the hematopoietic phenotype.
  
  
  CONCLUSIONS
  Our results provide the first in vivo evidence of an involvement of Numb and Numblike in zebrafish erythroid differentiation during primitive hematopoiesis. Furthermore, we found that, at least in part, the nb/nbl morphant phenotype is due to enhanced Notch activation within hematopoietic districts, which in turn results in primitive erythroid differentiation defects.
authors.affiliation: Dipartimento di Biologia, Università degli Studi di Milano, Milano, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Bresciani
authors.forename: Stefano
authors.initials: S
authors.lastname: Confalonieri
authors.forename: Solei
authors.initials: S
authors.lastname: Cermenati
authors.forename: Simona
authors.initials: S
authors.lastname: Cimbro
authors.forename: Efrem
authors.initials: E
authors.lastname: Foglia
authors.forename: Monica
authors.initials: M
authors.lastname: Beltrame
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Di Fiore
authors.forename: Franco
authors.initials: F
authors.lastname: Cotelli
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000166:cytology*; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D014176:Protein Biosynthesis; D051880:Receptors, Notch / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; D029961:Zebrafish Proteins; C559058:hspd1 protein, zebrafish; C513665:numb protein, zebrafish