The role of Notch in patterning the human vertebral column

Dunwoodie, Sally L.

doi:10.1016/j.gde.2009.06.005

Cited by 28 publications

(9 citation statements)

References 59 publications

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“…Conditional knockout of Dll1 (or Mindbomb1, a key co-factor for Dll1 activity) in neocortical progenitors recapitulates much of the phenotype observed in the Rbpsuh knockout (Kawaguchi et al, 2008c; Yoon et al, 2008), indicating that Dll1 is a major non-compensated Notch ligand in the neocortex. By contrast, while Dll3 exhibits specific functions during somitogenesis and T-cell development (Dunwoodie, 2009; Hoyne et al, 2011), there is no reported phenotype in the neocortex, similar to the cochlea and retina (Hartman et al, 2007; Nelson et al, 2009a), indicating possible compensatory mechanisms for Dll3 functions in the nervous system. These unique roles are further supported by evidence that Dll1-specific functions in the nervous system cannot be rescued by genetic replacement of Dll3 (Geffers et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Dynamic Interactions between Intermediate Neurogenic Progenitors and Radial Glia in Embryonic Mouse Neocortex: Potential Role in Dll1-Notch Signaling

et al. 2013

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The mammalian neocortical progenitor cell niche is composed of a diverse repertoire of neuroepithelial cells, radial glia (RG), and intermediate neurogenic progenitors (INPs). Previously, live-cell imaging experiments have proved crucial in identifying these distinct progenitor populations, especially INPs, which amplify neural output by undergoing additional rounds of proliferation before differentiating into new neurons. INPs also provide feedback to the RG pool by serving as a source of Delta-like 1 (Dll1), a key ligand for activating Notch signaling in neighboring cells, a well-known mechanism for maintaining RG identity. While much is known about Dll1-Notch signaling at the molecular level, little is known about how this cell-cell contact dependent feedback is transmitted at the cellular level. To investigate how RG and INPs might interact to convey Notch signals, we used high-resolution live-cell multiphoton microscopy (MPM) to directly observe cellular interactions and dynamics, in conjunction with Notch-pathway specific reporters in the neocortical neural stem cell niche in organotypic brain slices from embryonic mice. We found that INPs and RG interact via dynamic and transient elongate processes, some apparently long-range (extending from the subventricular zone to the ventricular zone), and some short-range (filopodia-like). Gene expression profiling of RG and INPs revealed further progenitor cell diversification, including different subpopulations of Hes1+ and/or Hes5+ RG, and Dll1+ and/or Dll3+ INPs. Thus, the embryonic progenitor niche includes a network of dynamic cell-cell interactions, utilizing different combinations of Notch signaling molecules to maintain and likely diversify progenitor pools.

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Section: Discussionmentioning

confidence: 99%

Dynamic Interactions between Intermediate Neurogenic Progenitors and Radial Glia in Embryonic Mouse Neocortex: Potential Role in Dll1-Notch Signaling

et al. 2013

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“…In addition to the clinically benign isolated vertebral defects seen in ALGS, mutations in several of the Notch signaling pathway genes cause severe vertebral and costal abnormalities in spondylocostal dysostosis (SCD, OMIM# 277300) and spondylothoracic dysostosis (STD). These latter diseases are grouped into the general category of abnormal vertebral segmentation (AVS) disorders characterized by congenital malformations in which the vertebrae are fused or altered in shape, position, or size [52]. AVS can be caused by genetic or environmental perturbations and can present with additional malformations or as an isolated abnormality.…”

Section: Spondylocostal Dysostosis (Scd) and Spondylothoracic Dysomentioning

confidence: 99%

Notch signaling in human development and disease

Penton

Leonard

Spinner

2012

Seminars in Cell & Developmental Biology

291

221

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Mutations in Notch signaling pathway members cause developmental phenotypes that affect the liver, skeleton, heart, eye, face, kidney, and vasculature. Notch associated disorders include the autosomal dominant, multi-system, Alagille syndrome caused by mutations in both a ligand (Jagged1 (JAG1)) and receptor (NOTCH2) and autosomal recessive spondylocostal dysostosis, caused by mutations in a ligand (Delta-like-3 (DLL3)), as well as several other members of the Notch signaling pathway. Mutations in NOTCH2 have also recently been connected to Hajdu-Cheney syndrome, a dominant disorder causing focal bone destruction, osteoporosis, craniofacial morphology and renal cysts. Mutations in the NOTCH1 receptor are associated with several types of cardiac disease and mutations in NOTCH3 cause the dominant adult onset disorder CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a vascular disorder with onset in the 4th or 5th decades. Studies of these human disorders and their inheritance patterns and types of mutations reveal insights into the mechanisms of Notch signaling.

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“…Although these structural features are critical for ligand signaling activity, losses in Dll3 are associated with vertebral segmentation and rib malformations similar to those caused by defects in Notch signaling (Dunwoodie, 2009). Dll3, however, does not bind Notch in trans or activate Notch signaling (Ladi et al, 2005), and the majority of Dll3 is detected in the Golgi, with relatively little, if any, cell surface expression (Geffers et al, 2007).…”

Section: Canonical Notch Ligand Structurementioning

confidence: 99%

Canonical and Non-Canonical Notch Ligands

D’Souza

Meloty-Kapella

Weinmaster

2010

Current Topics in Developmental Biology

304

274

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Notch signaling induced by canonical Notch ligands is critical for normal embryonic development and tissue homeostasis through the regulation of a variety of cell fate decisions and cellular processes. Activation of Notch signaling is normally tightly controlled by direct interactions with ligand-expressing cells and dysregulated Notch signaling is associated with developmental abnormalities and cancer. While canonical Notch ligands are responsible for the majority of Notch signaling, a diverse group of structurally unrelated non-canonical ligands has also been identified that activate Notch and likely contribute to the pleiotropic effects of Notch signaling. Soluble forms of both canonical and non-canonical ligands have been isolated, some of which block Notch signaling and could serve as natural inhibitors of this pathway. Ligand activity can also be indirectly regulated by other signaling pathways at the level of ligand expression, serving to spatio-temporally compartmentalize Notch signaling activity and integrate Notch signaling into a molecular network that orchestrates developmental events. Here, we review the molecular mechanisms underlying the dual role of Notch ligands as activators and inhibitors of Notch signaling. Additionally, evidence that Notch ligands function independent of Notch are presented. We also discuss how ligand post-translational modification, endocytosis, proteolysis and spatio-temporal expression regulate their signaling activity.

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The role of Notch in patterning the human vertebral column

Cited by 28 publications

References 59 publications

Dynamic Interactions between Intermediate Neurogenic Progenitors and Radial Glia in Embryonic Mouse Neocortex: Potential Role in Dll1-Notch Signaling

Dynamic Interactions between Intermediate Neurogenic Progenitors and Radial Glia in Embryonic Mouse Neocortex: Potential Role in Dll1-Notch Signaling

Notch signaling in human development and disease

Canonical and Non-Canonical Notch Ligands

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