Abstract
BackgroundThe dorsal root ganglion (DRG) is composed of well-characterized populations of sensory neurons and glia derived from a common pool of neural crest stem cells (NCCs), and is a good system to study the mechanisms of neurogenesis and gliogenesis. Notch signaling is known to play important roles in DRG development, but the full scope of Notch functions in mammalian DRG development remains poorly understood.ResultsIn the present study, we used Wnt1-Cre to conditionally inactivate the transcription factor Rbpj, a critical integrator of activation signals from all Notch receptors, in NCCs and their derived cells. Deletion of Rbpj caused the up-regulation of NeuroD1 and precocious neurogenesis in DRG early development but led to an eventual deficit of sensory neurons at later stages, due to reduced cell proliferation and abnormal cell death. In addition, gliogenesis was delayed initially, but a near-complete loss of glia was observed finally in Rbpj-deficient DRG. Furthermore, we found P75 and Sox10, which are normally expressed exclusively in neuronal and glial progenitors of the DRG after the NCCs have completed their migration, were co-expressed in many cells of the DRG of Rbpj conditional knock-out mice.ConclusionsOur data indicate that Rbpj-mediated canonical Notch signaling inhibits DRG neuronal differentiation, possibly by regulating NeuroD1 expression, and is required for DRG gliogenesis in vivo.
Highlights
The dorsal root ganglion (DRG) is composed of well-characterized populations of sensory neurons and glia derived from a common pool of neural crest stem cells (NCCs), and is a good system to study the mechanisms of neurogenesis and gliogenesis
We found that Ngn1 and Ngn2 expression was unchanged in the absence of Rbpj, but Neurogenic differentiation 1 (NeuroD1) was up-regulated and precocious neurogenesis occurred in the DRG
Most P75+ NCCs were positively labeled with bgal antibody in both Rbpj conditional knock-out (CKO) (Wnt1-Cre;Rbpjflox/flox; Rosa26R) and control (Wnt1-Cre;Rosa26R) embryos (Figure 1A-F), demonstrating that Rbpj could be deleted in NCCs and their derivatives from E9.5 on
Summary
The dorsal root ganglion (DRG) is composed of well-characterized populations of sensory neurons and glia derived from a common pool of neural crest stem cells (NCCs), and is a good system to study the mechanisms of neurogenesis and gliogenesis. The nervous system is made up of a wide variety of neuronal and glial cell types. The dorsal root ganglion (DRG), which consists of several well-characterized types of sensory neurons and glial cells, is an attractive model system to investigate the molecular processes underlying cellular differentiation in the nervous system [1]. Many genes are involved in the generation of sensory neurons and glia from multipotent NCCs. Among the various cell-surface proteins known to be expressed by NCCs, the low affinity neurotrophin receptor P75 has been widely used to identify and isolate NCCs [7]. Sensory neuron subtypes with distinct modalities acquire specific patterns of Trk expression, uniquely expressing either TrkA, TrkB, or TrkC [1,15]
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