Notch signaling controls the balance of ciliated and secretory cell fates in developing airways

Notch signaling mediates numerous developmental cell fate decisions in organisms ranging from flies to humans, resulting in the generation of multiple cell types from equipotential precursors. In this paper, we present evidence that activation of Notch by its ligand Serrate apportions myogenic and non-myogenic cell fates within the early Xenopus heart field. The crescent-shaped field of heart mesoderm is specified initially as cardiomyogenic. While the ventral region of the field forms the myocardial tube, the dorsolateral portions lose myogenic potency and form the dorsal mesocardium and pericardial roof (Raffin, M., Leong, L. M., Rones, M. S., Sparrow, D., Mohun, T. and Mercola, M. (2000) Dev. Biol., 218, 326–340). The local interactions that establish or maintain the distinct myocardial and non-myocardial domains have never been described. Here we show that Xenopus Notch1 (Xotch) and Serrate1 are expressed in overlapping patterns in the early heart field. Conditional activation or inhibition of the Notch pathway with inducible dominant negative or active forms of the RBP-J/Suppressor of Hairless [Su(H)] transcription factor indicated that activation of Notch feeds back on Serrate1 gene expression to localize transcripts more dorsolaterally than those of Notch1, with overlap in the region of the developing mesocardium. Moreover, Notch pathway activation decreased myocardial gene expression and increased expression of a marker of the mesocardium and pericardial roof, whereas inhibition of Notch signaling had the opposite effect. Activation or inhibition of Notch also regulated contribution of individual cells to the myocardium. Importantly, expression of Nkx2. 5 and Gata4 remained largely unaffected, indicating that Notch signaling functions downstream of heart field specification. We conclude that Notch signaling through Su(H) suppresses cardiomyogenesis and that this activity is essential for the correct specification of myocardial and non-myocardial cell fates.

NOTCH Signaling Is Required for Formation and Self-Renewal of Tumor-Initiating Cells and for Repression of Secretory Cell Differentiation in Colon Cancer

Cancer Research ◽

10.1158/0008-5472.can-09-2557 ◽

2010 ◽

Vol 70 (4) ◽

pp. 1469-1478 ◽

Cited By ~ 182

Author(s):

S. S. Sikandar ◽

K. T. Pate ◽

S. Anderson ◽

D. Dizon ◽

R. A. Edwards ◽

...

Keyword(s):

Colon Cancer ◽

Cell Differentiation ◽

Notch Signaling ◽

Secretory Cell ◽

Tumor Initiating Cells ◽

Self Renewal

A role for Notch signaling in the interpretation of cell fates in a morphogen gradient

Developmental Biology ◽

10.1016/j.ydbio.2006.04.312 ◽

2006 ◽

Vol 295 (1) ◽

pp. 427

Author(s):

Leonard Dobens ◽

Benjamin Levine

Keyword(s):

Notch Signaling ◽

Morphogen Gradient ◽

Cell Fates

Sibling cell fate in the Drosophila adult external sense organ lineage is specified by prospero function, which is regulated by Numb and Notch

Development ◽

10.1242/dev.126.10.2083 ◽

1999 ◽

Vol 126 (10) ◽

pp. 2083-2092 ◽

Cited By ~ 9

Author(s):

G.V. Reddy ◽

V. Rodrigues

Keyword(s):

Transcription Factor ◽

Notch Signaling ◽

Cell Fate ◽

Sense Organ ◽

Sensory Organ ◽

Sensory Organs ◽

Cell Fates ◽

Homeodomain Transcription Factor ◽

Intrinsic Signal ◽

Sensory Organ Precursors

Specification of cell fate in the adult sensory organs is known to be dependent on intrinsic and extrinsic signals. We show that the homeodomain transcription factor Prospero (Pros) acts as an intrinsic signal for the specification of cell fates within the mechanosensory lineage. The sensory organ precursors divide to give rise to two secondary progenitors - PIIa and PIIb. Pros is expressed in PIIb, which gives rise to the neuron and thecogen cells. Loss of Pros function affects the identity of PIIb and neurons fail to differentiate. Pros misexpression is sufficient for the transformation of PIIa to PIIb fate. The expression of Pros in the normal PIIb cell appears to be regulated by Notch signaling.

Sanpodo controls sensory organ precursor fate by directing Notch trafficking and binding γ-secretase

The Journal of Cell Biology ◽

10.1083/jcb.201209023 ◽

2013 ◽

Vol 201 (3) ◽

pp. 439-448 ◽

Cited By ~ 13

Author(s):

Alok Upadhyay ◽

Vasundhara Kandachar ◽

Diana Zitserman ◽

Xin Tong ◽

Fabrice Roegiers

Keyword(s):

Notch Signaling ◽

Cell Fate ◽

Daughter Cell ◽

Asymmetric Cell Division ◽

Notch Receptor ◽

Receptor Internalization ◽

Sensory Organ ◽

Cell Fates ◽

Cellular Context ◽

Sensory Organ Precursor

In Drosophila peripheral neurogenesis, Notch controls cell fates in sensory organ precursor (SOP) cells. SOPs undergo asymmetric cell division by segregating Numb, which inhibits Notch signaling, into the pIIb daughter cell after cytokinesis. In contrast, in the pIIa daughter cell, Notch is activated and requires Sanpodo, but its mechanism of action has not been elucidated. As Sanpodo is present in both pIIa and pIIb cells, a second role for Sanpodo in regulating Notch signaling in the low-Notch pIIb cell has been proposed. Here we demonstrate that Sanpodo regulates Notch signaling levels in both pIIa and pIIb cells via distinct mechanisms. The interaction of Sanpodo with Presenilin, a component of the γ-secretase complex, was required for Notch activation and pIIa cell fate. In contrast, Sanpodo suppresses Notch signaling in the pIIb cell by driving Notch receptor internalization. Together, these results demonstrate that a single protein can regulate Notch signaling through distinct mechanisms to either promote or suppress signaling depending on the local cellular context.

Forkhead box N4 (Foxn4) activates Dll4-Notch signaling to suppress photoreceptor cell fates of early retinal progenitors

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1115767109 ◽

2012 ◽

Vol 109 (9) ◽

pp. E553-E562 ◽

Cited By ~ 45

Author(s):

H. Luo ◽

K. Jin ◽

Z. Xie ◽

F. Qiu ◽

S. Li ◽

...

Keyword(s):

Notch Signaling ◽

Photoreceptor Cell ◽

Cell Fates ◽

Forkhead Box

Notch Signaling in Development, Tissue Homeostasis, and Disease

Physiological Reviews ◽

10.1152/physrev.00005.2017 ◽

2017 ◽

Vol 97 (4) ◽

pp. 1235-1294 ◽

Cited By ~ 209

Author(s):

Chris Siebel ◽

Urban Lendahl

Keyword(s):

Notch Signaling ◽

Cell Communication ◽

Cell Types ◽

The Body ◽

Tissue Homeostasis ◽

Cell Fates ◽

Signaling Mechanism ◽

Transmembrane Receptors ◽

Notch Gene ◽

Broad Variety

Notch signaling is an evolutionarily highly conserved signaling mechanism, but in contrast to signaling pathways such as Wnt, Sonic Hedgehog, and BMP/TGF-β, Notch signaling occurs via cell-cell communication, where transmembrane ligands on one cell activate transmembrane receptors on a juxtaposed cell. Originally discovered through mutations in Drosophila more than 100 yr ago, and with the first Notch gene cloned more than 30 yr ago, we are still gaining new insights into the broad effects of Notch signaling in organisms across the metazoan spectrum and its requirement for normal development of most organs in the body. In this review, we provide an overview of the Notch signaling mechanism at the molecular level and discuss how the pathway, which is architecturally quite simple, is able to engage in the control of cell fates in a broad variety of cell types. We discuss the current understanding of how Notch signaling can become derailed, either by direct mutations or by aberrant regulation, and the expanding spectrum of diseases and cancers that is a consequence of Notch dysregulation. Finally, we explore the emerging field of Notch in the control of tissue homeostasis, with examples from skin, liver, lung, intestine, and the vasculature.

Antagonistic actions of Olig2 and the Notch signaling pathway in the assignment of neuronal and glial cell fates

Developmental Biology ◽

10.1016/j.ydbio.2009.05.022 ◽

2009 ◽

Vol 331 (2) ◽

pp. 389

Author(s):

Lin Lin Yang ◽

Zachary B. Gaber ◽

Steven E. Weicksel ◽

Eric Dessaud ◽

David L. Rousso ◽

...

Keyword(s):

Notch Signaling ◽

Signaling Pathway ◽

Glial Cell ◽

Notch Signaling Pathway ◽

Cell Fates