Cell-cell interactions define a quintessential aspect of multicellular development. Metazoan morphogenesis depends on a handful of fundamental, conserved cellular interaction mechanisms, one of which is defined by the Notch signaling pathway. Signals transmitted through the Notch surface receptor have a unique developmental role: Notch signaling links the fate of one cell with that of a cellular neighbor through physical interactions between the Notch receptor and the membrane-bound ligands that are expressed in an apposing cell. The developmental outcome of Notch signals is strictly dependent on the cellular context and can influence differentiation, proliferation and apoptotic cell fates. The Notch pathway is conserved across species (Artavanis-Tsakonas et al., 1999; Bray, 2006; Kopan and Ilagan, 2009). In humans, Notch malfunction has been associated with a diverse range of diseases linked to changes in cell fate and cell proliferation including cancer (Louvi and Artavanis-Tsakonas, 2012). In this Cell Science at a Glance article and the accompanying poster we summarize the molecular biology of Notch signaling, its role in development and its relevance to disease.
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http://dx.doi.org/10.1242/jcs.127308 | DOI Listing |
Biol Open
January 2025
Faculty of Biology Medicine and Health, The University of Manchester, Manchester M13 9PT, UK.
In the developing mouse ventral spinal cord, HES5, a transcription factor downstream of Notch signalling, is expressed as evenly spaced clusters of high HES5-expressing neural progenitor cells along the dorsoventral axis. While Notch signalling requires direct membrane contact for its activation, we have previously shown mathematically that contact needs to extend beyond neighbouring cells for the HES5 pattern to emerge. However, the presence of cellular structures that could enable such long-distance signalling was unclear.
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Hormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt.
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National Clinical Research Center for TCM Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
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View Article and Find Full Text PDFNat Commun
January 2025
Department of Biomedical Engineering, Boston University, Boston, MA, USA.
Synthetic Notch (SynNotch) receptors function like natural Notch proteins and can be used to install customized sense-and-respond capabilities into mammalian cells. Here, we introduce an adaptor-based strategy for regulating SynNotch activity via fluorescein isomers and analogs. Using an optimized fluorescein-binding SynNotch receptor, we describe ways to chemically control SynNotch signaling, including an approach based on a bio-orthogonal chemical ligation and a spatially controllable strategy via the photo-patterned uncaging of an o-nitrobenzyl-caged fluorescein conjugate.
View Article and Find Full Text PDFHow specification mechanisms that generate neural diversity translate into specific neuronal targeting, connectivity, and function in the adult brain is not understood. In the medulla region of the optic lobe, neural progenitors generate different neurons in a fixed order by sequentially expressing a series of temporal transcription factors as they age. Then, Notch signaling in intermediate progenitors further diversifies neuronal progeny.
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