Notch Activation Regulates the Segregation and Differentiation of Rhombomere Boundary Cells in the Zebrafish Hindbrain

Abstract

During segmentation of the vertebrate hindbrain, a distinct population of boundary cells forms at the interface between each segment. Little is known regarding mechanisms that regulate the formation or functions of these cells. We have investigated a potential role of Notch signaling and find that in the zebrafish hindbrain, radical fringe is expressed in boundary cells and delta genes are expressed adjacent to boundaries, consistent with a sustained activation of Notch in boundary cells. Mosaic expression experiments reveal that activation of the Notch/Su(H) pathway regulates cell affinity properties that segregate cells to boundaries. In addition, Notch signaling correlates with a delayed neurogenesis at hindbrain boundaries and is required to inhibit premature neuronal differentiation of boundary cells. These findings reveal that Notch activation couples the regulation of location and differentiation in hindbrain boundary cells. Such coupling may be important for these cells to act as a stable signaling center.

Sequence and embryonic expression of three zebrafish fringe genes: lunatic fringe, radical fringe, and manic fringe

“…This finding suggests that normal rfng expression in the hindbrain depends on positive regulation by Notch activity, suggesting the existence of a positive feedback loop tending to reinforce rfng expression at these sites. Taken together, these findings raise the interesting possibility that Notch signaling is involved in rhombomere boundary formation-a hypothesis that we have explored and confirmed in a separate paper with Cheng et al (2004). In accord with this hypothesis, we also find that the expression of mariposa is disorderly in mib mutants (Fig.…”

Cochlear supporting cell transdifferentiation and integration into hair cell layers by inhibition of ephrin-B2 signalling

“…Therefore, as shown during vasculogenesis 40,41 , ephrin-B2 could be a downstream target of Notch signalling in supporting cells required to segregate the latter cells from adjacent hair cells. In support of this hypothesis, it was proposed that Notch signalling couples cell segregation and differentiation at hindbrain boundaries 42,43 . As a consequence, loss of a Notch pathway component could weaken the supporting cell fate and make easier the switch towards the hair cell phenotype.…”

Polysialyltransferase expression is linked to neuronal migration in the developing and adult zebrafish

“…The pst expression is found in the hindbrain reaching from the dorsally positioned lower rhombic lip, which also expresses high levels of stx, toward the floorplate along the central domains of each rhombomere, where neuronal differentiation occurs (Cheng et al, 2004). At 4 days of embryonic development, expression of both polysialyltransferases has declined to minute amounts.…”