Delta/Notch signaling controls neuroepithelial morphogenesis in the zebrafish spinal cord

Abstract

The morphogenesis of the nervous system requires coordinating the specification and differentiation of neural precursor cells, the establishment of neuroepithelial tissue architecture and the execution of specific cellular movements. How these aspects of neural development are linked is incompletely understood. Here we inactivate a major regulator of embryonic neurogenesis -the Delta/Notch pathway -and analyze the effect on zebrafish central nervous system morphogenesis. While some parts of the nervous system can establish neuroepithelial tissue architecture independently of Notch, Notch signaling is essential for spinal cord morphogenesis. In this tissue, Notch signaling is required to repress neuronal differentiation and promote neuroepithelial apico-basal polarity. Concomitant with a loss of their neuroepithelial properties, Notch signaling deficient cells also alter their morphogenetic behavior. In the wild-type zebrafish neural tube, cells divide at the organ midline to contribute one daughter cell to each organ half. Notch deficient animals fail to display this behavior and therefore form a misproportioned spinal cord. Taken together, our findings show that Notch signaling governs not only the cellular composition but also the morphogenetic shaping of the zebrafish spinal cord.

A quantitative biophysical principle to explain the 3D cellular connectivity in curved epithelia

“…The latter links the activation energy needed to recruit additional neighbors with geometrical descriptors (i.e., tissue thickness/curvature). Our results provide new biological insight into the spatiotemporal regulation of cell-cell connectivity, a property that ultimately regulates juxtracrine signaling and is pivotal for primordia patterning and cell fate determination (Sharma et al, 2019;Tung et al, 2012). In this context, our study points towards an effect of scutoids on the regulation of the physiological properties of tissues.…”

“…This formula implies that polygonal cells in packed tissues, on average, have six neighbors (i.e., the average 2D cellular connectivity reads ‫݊ۃ‬ ଶ ‫ۄ‬ ൌ 6). As for its biological consequences, the degree of cellular connectivity determines, for example, the strength of the cell-cell juxtracrine signaling (Tung et al, 2012;Sharma et al, 2019;Perrimon et al, 2012). Not surprisingly, the validity of this connectivity principle to the third dimension has been taken for granted since the role played by apico-basal cell intercalations has been disregarded and cells have been assumed to have prismatic-like shapes in either planar or bent epithelia.…”

A quantitative biophysical principle to explain the 3D cellular connectivity in curved epithelia

“…As for the broader implications of our findings, our results provide new biological insight into the regulation of cell-cell connectivity in curved tissues. This property ultimately regulates juxtracrine signaling, and is pivotal for early development, primordia patterning, and cell fate determination (Guignard et al, 2020; Sharma et al, 2019; Tung et al, 2012). Moreover, recent research has shown that cellular connectivity regulates the viscosity of tissues (Petridou et al, 2021).…”

“…This principle states that polygonal 17 cells in packed tissues, on average, have six neighbors (i.e., the average 2D ). As for its biological consequences, the 19 degree of cellular connectivity determines, for example, the strength of the 20 cell-cell juxtracrine signaling (Tung et al, 2012;Sharma et al, 2019;Perrimon 21 et al, 2012). Not surprisingly, the validity of this connectivity principle to the 22 third dimension has been taken for granted since the role played by apico-23 basal cell intercalations has been disregarded and cells have been assumed 24…”

“…This formula implies that cells in packed tissues have, on average, six neighbors (i.e., the average cellular connectivity on a surface reads 〈 n 2 D 〉 = 6) (Reinhardt, 1918; Wetzel, 1926). This principle has biological consequences, for example, the degree of cellular connectivity regulates the strength of the cell-cell juxtracrine signaling (Guignard et al, 2020; Sharma et al, 2019; Tung et al, 2012).…”