Faster embryonic segmentation through elevated Delta-Notch signalling

Abstract

An important step in understanding biological rhythms is the control of period. A multicellular, rhythmic patterning system termed the segmentation clock is thought to govern the sequential production of the vertebrate embryo's body segments, the somites. Several genetic loss-of-function conditions, including the Delta-Notch intercellular signalling mutants, result in slower segmentation. Here, we generate DeltaD transgenic zebrafish lines with a range of copy numbers and correspondingly increased signalling levels, and observe faster segmentation. The highest-expressing line shows an altered oscillating gene expression wave pattern and shortened segmentation period, producing embryos with more, shorter body segments. Our results reveal surprising differences in how Notch signalling strength is quantitatively interpreted in different organ systems, and suggest a role for intercellular communication in regulating the output period of the segmentation clock by altering its spatial pattern.

Excitable Dynamics and Yap-Dependent Mechanical Cues Drive the Segmentation Clock

“…In mouse somitogenesis, the role of Notch signaling has been controversial: while blocking the pathway in embryos leads to the disappearance of Lfng oscillations (Barrantes et al, 1999; Ferjentsik et al, 2009), other studies reported that oscillations are maintained but desynchronized when Notch is inhibited (Okubo et al, 2012; Tsiairis and Aulehla, 2016). Notch1 and DLL1 oscillations could underlie the pulse dynamics (Bone et al, 2014; Kim et al, 2011; Liao et al, 2016; Shimojo and Kageyama, 2016). However, restoration of non-oscillatory expression of DLL1 in the mouse PSM leads to the formation of normal somites (Preusse et al, 2015).…”

Delta-Notch signalling in segmentation

“…In zebrafish, a 20% longer segmentation period was observed in the anterior somites in deltaD and mind bomb mutants and in DAPT-treated embryos (Herrgen et al., 2010). Conversely, the segmentation period could be shortened about 6.5% in transgenic line, Damascus , carrying multiple copies of deltaD-yfp (Liao et al., 2016). In zebrafish, more Notch signalling speeds the clock up, and less slows it down.…”

“…As mentioned above in Section 3.2, the zebrafish Damascus transgenic line carries approximately 100 deltaD-venus / yfp transgene copies and showed higher Notch signalling strength and a faster segmentation rate in the embryo (Liao et al., 2016). The PSM length decreases at the same rate as in wildtype, but the anterior wavelength of the her1 gene expression waves in Damascus is about 20% shorter than in wildtype.…”

“…7) (Liao et al., 2016). At the gene expression level, DeltaD protein in the posterior PSM was well correlated to its gene copy number, but only copy numbers on the extremes of the range (the null mutant with zero copies and damascus with ∼100 copies) showed a change in segmentation period or segment boundary defects.…”

CDK 1 and CDK 2 regulate NICD 1 turnover and the periodicity of the segmentation clock

“…Most studies addressing the molecular mechanisms regulating the periodicity of clock gene oscillations have focused on the role of Notch signalling components [10,19,[21][22][23][24][25].…”