Editing Notch signaling pathway (section)

=== Role in somitogenesis ===
{{anchor|Segmentation}}

Notch signaling is central to [[somitogenesis]]. In 1995, Notch1 was shown to be important for coordinating the segmentation of somites in mice.<ref name="Conlon RA, Reaume AG, Rossant J 1995 1533–45">{{cite journal | vauthors = Conlon RA, Reaume AG, Rossant J | title = Notch1 is required for the coordinate segmentation of somites | journal = Development | volume = 121 | issue = 5 | pages = 1533–1545 | date = May 1995 | pmid = 7789282 | doi = 10.1242/dev.121.5.1533 }}</ref> Further studies identified the role of Notch signaling in the segmentation clock. These studies hypothesized that the primary function of Notch signaling does not act on an individual cell, but coordinates cell clocks and keep them synchronized. This hypothesis explained the role of Notch signaling in the development of segmentation and has been supported by experiments in mice and zebrafish.<ref>{{cite journal | vauthors = Hrabĕ de Angelis M, McIntyre J, Gossler A | title = Maintenance of somite borders in mice requires the Delta homologue DII1 | journal = Nature | volume = 386 | issue = 6626 | pages = 717–721 | date = April 1997 | pmid = 9109488 | doi = 10.1038/386717a0 | s2cid = 4331445 | bibcode = 1997Natur.386..717D }}</ref><ref>{{cite journal | vauthors = van Eeden FJ, Granato M, Schach U, Brand M, Furutani-Seiki M, Haffter P, Hammerschmidt M, Heisenberg CP, Jiang YJ, Kane DA, Kelsh RN, Mullins MC, Odenthal J, Warga RM, Allende ML, Weinberg ES, Nüsslein-Volhard C | display-authors = 6 | title = Mutations affecting somite formation and patterning in the zebrafish, Danio rerio | journal = Development | volume = 123 | pages = 153–164 | date = December 1996 | pmid = 9007237 | doi = 10.1242/dev.123.1.153 }}</ref><ref>{{cite journal | vauthors = Huppert SS, Ilagan MX, De Strooper B, Kopan R | title = Analysis of Notch function in presomitic mesoderm suggests a gamma-secretase-independent role for presenilins in somite differentiation | journal = Developmental Cell | volume = 8 | issue = 5 | pages = 677–688 | date = May 2005 | pmid = 15866159 | doi = 10.1016/j.devcel.2005.02.019 | doi-access = free }}</ref> Experiments with Delta1 mutant mice that show abnormal somitogenesis with loss of anterior/posterior polarity suggest that Notch signaling is also necessary for the maintenance of somite borders.<ref name="Conlon RA, Reaume AG, Rossant J 1995 1533–45" />

During [[somitogenesis]], a molecular oscillator in [[paraxial mesoderm]] cells dictates the precise rate of somite formation. A [[clock and wavefront model]] has been proposed in order to spatially determine the location and boundaries between [[somites]]. This process is highly regulated as somites must have the correct size and spacing in order to avoid malformations within the axial skeleton that may potentially lead to [[spondylocostal dysostosis]]. Several key components of the Notch signaling pathway help coordinate key steps in this process. In mice, mutations in Notch1, Dll1 or Dll3, Lfng, or Hes7 result in abnormal somite formation. Similarly, in humans, the following mutations have been seen to lead to development of spondylocostal dysostosis: DLL3, LFNG, or HES7.<ref>{{cite journal | vauthors = Wahi K, Bochter MS, Cole SE | title = The many roles of Notch signaling during vertebrate somitogenesis | journal = Seminars in Cell & Developmental Biology | volume = 49 | pages = 68–75 | date = January 2016 | pmid = 25483003 | doi = 10.1016/j.semcdb.2014.11.010 | s2cid = 10822545 }}</ref>