Protrusion-Mediated Signaling Regulates Patterning of the Developing Nervous System

Abstract

During brain development, the tissue pattern and specification are the foundation of neuronal circuit formation. Contact-mediated lateral inhibition is well known to play an important role in determining cell fate decisions in the nervous system by either regulating tissue boundary formation or the classical salt-and-pepper pattern of differentiation that results from direct neighboring cell contacts. In many systems, however, such as the Drosophila notum, Drosophila wing, zebrafish pigmented cells, and zebrafish spinal cord, the differentiation pattern occurs at multiple-cell diameter distances. In this review, we discuss the evidence and characteristics of long-distance patterning mechanisms mediated by cellular protrusions. In the nervous system, cellular protrusions deliver the Notch ligand Delta at long range to prevent cells from differentiating in their vicinity. By temporal control of protrusive activity, this mechanism can pattern differentiation in both space and time.

Dynamic switching of lateral inhibition spatial patterns

“…The first addition is extending the LI signalling distance between cells, inspired by the modelling work that shows how protrusions can extend Notch signalling distance, which leads to longer period spatial patterns [18]. This is in line with experimental observations of filopodia in Drosophila, which have been shown to carry Notch ligands and induce Notch signalling several cell diameters away [17,24], and various literature points to the existence of protrusions in the neuroepithelia that are probably capable of Notch signalling [25][26][27][28]. The second addition to the model is the introduction of a differentiation process that alters the amount of Notch signalling that neighbouring cells receive from a differentiating cell.…”

A lateral protrusion latticework connects neuroepithelial cells and is regulated during neurogenesis

“…Later, in the neural tube, the Notch ligand Delta is presented by transient basally originating cell protrusions produced by newborn neurons to regulate the spatial and temporal production of spinal cord neurons ( Hadjivasiliou et al, 2019 , 2016 ). A correlation between filopodia and Notch ligand presentation has also been identified in the mouse cortex ( Moore et al, 2020 ; Nelson et al, 2013 ), whereas other work supports a dependence on apical adherens junction-localised Notch ligands in chick and mouse neuroepithelium ( Hatakeyama et al, 2014 ). The former findings with respect to Wnt signalling, and others reporting presentation of further ligands or their receptors, including sonic hedgehog, bone morphogenetic proteins and fibroblast growth factors, in non-neural contexts ( Huang et al, 2019 ; Roy et al, 2014 ; Sanders et al, 2013 ) raise an alternative or complementary hypothesis to the notion that signal diffusion through extracellular space underlies establishment of signalling gradients that pattern developing tissues ( Briscoe and Small, 2015 ; Kornberg, 2014 ; Wolpert, 2016 ).…”

A lateral protrusion latticework connects neuroepithelial cells and is regulated during neurogenesis

“…Later, in the neural tube, the Notch ligand Delta, is presented by transient basally originating cell protrusions produced by newborn neurons to regulate the spatial and temporal production for spinal cord neurons (Hadjivasiliou et al, 2019). A correlation between filopodia and Notch ligand presentation has also been identified in the mouse cortex (Moore et al, 2020;Nelson et al, 2013), while other work supports a dependence on apical adherens junction localised Notch ligands in chick and mouse neuroepithelium (Hatakeyama et al, 2014). The former findings with respect to Wnt signalling and others reporting presentation of further ligands or their receptors, including Sonic hedgehog, Bone morphogenetic protein and Fibroblast growth factor, in non-neural contexts (Huang et al, 2019;Roy et al, 2014;Sanders et al, 2013) raise an alternative or complementary hypothesis to the notion that signal diffusion through extracellular space underlies establishment of signalling gradients which pattern developing tissues (Briscoe and Small, 2015;Kornberg, 2014;Wolpert, 2016).…”