title: Intralineage directional Notch signaling regulates self-renewal and differentiation of asymmetrically dividing radial glia.
abstract: Asymmetric division of progenitor/stem cells generates both self-renewing and differentiating progeny and is fundamental to development and regeneration. How this process is regulated in the vertebrate brain remains incompletely understood. Here, we use time-lapse imaging to track radial glia progenitor behavior in the developing zebrafish brain. We find that asymmetric division invariably generates a basal self-renewing daughter and an apical differentiating sibling. Gene expression and genetic mosaic analysis further show that the apical daughter is the source of Notch ligand that is essential to maintain higher Notch activity in the basal daughter. Notably, establishment of this intralineage and directional Notch signaling requires the intrinsic polarity regulator Partitioning defective protein-3 (Par-3), which segregates the fate determinant Mind bomb unequally to the apical daughter, thereby restricting the self-renewal potential to the basal daughter. These findings reveal with single-cell resolution how self-renewal and differentiation become precisely segregated within asymmetrically dividing neural progenitor/stem lineages.
authors.affiliation: Programs in Human Genetics and Biological Sciences, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143-2811, USA.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Dong
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.forename: Sang-Yeob
authors.initials: SY
authors.lastname: Yeo
authors.forename: Ajay
authors.initials: A
authors.lastname: Chitnis
authors.forename: Su
authors.initials: S
authors.lastname: Guo
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division / Q000502:physiology*; D019070:Cell Lineage; D016764:Cell Polarity; D004625:Embryo, Nonmammalian; D020869:Gene Expression Profiling; D055495:Neurogenesis / Q000502:physiology; D009457:Neuroglia / Q000166:cytology* / Q000502:physiology; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology*; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000502:physiology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology
chemical_list: D051880:Receptors, Notch; D029961:Zebrafish Proteins; D044767:Ubiquitin-Protein Ligases; C471932:mib1 protein, zebrafish