title: Selective neuronal lineages derived from Dll4-expressing progenitors/precursors in the retina and spinal cord.
abstract: BACKGROUND
  During retinal and spinal cord neurogenesis, Notch signaling plays crucial roles in regulating proliferation and differentiation of progenitor cells. One of the Notch ligands, Delta-like 4 (Dll4), has been shown to be expressed in subsets of retinal and spinal cord progenitors/precursors and involved in neuronal subtype specification. However, it remains to be determined whether Dll4 expression has any progenitor/precursor-specificity contributing to its functional specificity during neural development.
  
  
  RESULTS
  We generated a Dll4-Cre BAC transgenic mouse line that drives Cre recombinase expression mimicking that of the endogenous Dll4 in the developing retina and spinal cord. By fate-mapping analysis, we found that Dll4-expressing progenitors/precursors give rise to essentially all cone, amacrine and horizontal cells, a large portion of rod and ganglion cells, but only few bipolar and Müller cells. In the spinal cord, Dll4-expressing progenitors/precursors generate almost all V2a and V2c cells while producing only a fraction of the cells for other interneuron and motor neuron subtypes along the dorsoventral axis.
  
  
  CONCLUSIONS
  Our data suggest that selective expression of Dll4 in progenitors/precursors contributes to its functional specificity in neuronal specification and that the Dll4-Cre line is a valuable tool for gene manipulation to study Notch signaling.
authors.affiliation: Center for Advanced Biotechnology and Medicine and Department of Pediatrics, Rutgers University-Robert Wood Johnson Medical School, Piscataway, New Jersey.
authors.forename: Min
authors.initials: M
authors.lastname: Zou
authors.forename: Huijun
authors.initials: H
authors.lastname: Luo
authors.forename: Mengqing
authors.initials: M
authors.lastname: Xiang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002135:Calcium-Binding Proteins; D019070:Cell Lineage / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C519665:DLL4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins
keywords: Dll4; Notch signaling; V2 interneuron; neuronal lineage; retina; spinal cord