Physiological Notch signaling promotes gliogenesis in the developing peripheral and central nervous systems.
Constitutive activation of the Notch pathway can promote gliogenesis by peripheral (PNS) and central (CNS) nervous system progenitors. This raises the question of whether physiological Notch signaling regulates gliogenesis in vivo. To test this, we conditionally deleted Rbpsuh (Rbpj) from mouse PNS or CNS progenitors using Wnt1-Cre or Nestin-Cre. Rbpsuh encodes a DNA-binding protein (RBP/J) that is required for canonical signaling by all Notch receptors. In most regions of the developing PNS and spinal cord, Rbpsuh deletion caused only mild defects in neurogenesis, but severe defects in gliogenesis. These resulted from defects in glial specification or differentiation, not premature depletion of neural progenitors, because we were able to culture undifferentiated progenitors from the PNS and spinal cord despite their failure to form glia in vivo. In spinal cord progenitors, Rbpsuh was required to maintain Sox9 expression during gliogenesis, demonstrating that Notch signaling promotes the expression of a glial-specification gene. These results demonstrate that physiological Notch signaling is required for gliogenesis in vivo, independent of the role of Notch in the maintenance of undifferentiated neural progenitors.
Taylor
Merritt K
MK
Howard Hughes Medical Institute, Life Sciences Institute, Department of Internal Medicine, and Center for Stem Cell Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA.
Yeager
Kelly
K
Morrison
Sean J
SJ
D000818:Animals; D002454:Cell Differentiation; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D017950:Ganglia, Sensory / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D006609:High Mobility Group Proteins / Q000378:metabolism; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009457:Neuroglia / Q000166:cytology* / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism*; D055758:SOX9 Transcription Factor; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D014157:Transcription Factors / Q000378:metabolism; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism
D006609:High Mobility Group Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; C497571:Rbpj protein, mouse; D051880:Receptors, Notch; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D014157:Transcription Factors; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; C045073:Cre recombinase; D019426:Integrases