Regulation of size and scale in vertebrate spinal cord development

Abstract

All vertebrates have a spinal cord with dimensions and shape specific to their species. Yet how species‐specific organ size and shape are achieved is a fundamental unresolved question in biology. The formation and sculpting of organs begins during embryonic development. As it develops, the spinal cord extends in anterior–posterior direction in synchrony with the overall growth of the body. The dorsoventral (DV) and apicobasal lengths of the spinal cord neuroepithelium also change, while at the same time a characteristic pattern of neural progenitor subtypes along the DV axis is established and elaborated. At the basis of these changes in tissue size and shape are biophysical determinants, such as the change in cell number, cell size and shape, and anisotropic tissue growth. These processes are controlled by global tissue‐scale regulators, such as morphogen signaling gradients as well as mechanical forces. Current challenges in the field are to uncover how these tissue‐scale regulatory mechanisms are translated to the cellular and molecular level, and how regulation of distinct cellular processes gives rise to an overall defined size. Addressing these questions will help not only to achieve a better understanding of how size is controlled, but also of how tissue size is coordinated with the specification of pattern. This article is categorized under: Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and Timing Signaling Pathways > Global Signaling Mechanisms Nervous System Development > Vertebrates: General Principles

A dynamic, spatially periodic, micro‐pattern of HES5 underlies neurogenesis in the mouse spinal cord

“…We tested the model hypothesis that by changing the HES5 spatiotemporal pattern through tuning the coupling strength, the tissue is able to fine tune the rate of neurogenesis. We compared the motorneuron and interneuron progenitor domains as these two neighbouring domains in the D‐V axis are known to have different rates of differentiation (Kicheva et al, 2014; Kuzmicz‐Kowalska & Kicheva, 2020). Indeed, we find that that in the MN domain where the rate of differentiation is highest at E10.5, the HES5 and NGN2 pattern most closely matches the alternating high–low pattern (Fig 8I, MN).…”

A dynamic, spatially periodic, micro-pattern of HES5 underlies neurogenesis in the mouse spinal cord

“…We tested the hypothesis that by changing the HES5 spatiotemporal pattern through tuning the coupling strength, the tissue is able to fine tune the rate of neurogenesis. We compared the motorneuron and interneuron progenitor domains as these two neighbouring domains in the D-V axis are known to have different rates of differentiation (Kicheva et al, 2014;Kuzmicz-Kowalska & Kicheva, 2020). Indeed, we find that that in the MN domain where the rate of differentiation is highest at E10.5, the HES5 pattern most closely matches the saltand-pepper pattern (Figure 8, MN).…”

G1 Phase Lengthening During Neural Tissue Development Involves CDC25B Induced G1 Heterogeneity

“…Lengthening of the G1 phase has long been associated with neurogenesis (Kuzmicz-Kowalska and Kicheva, 2020; Molina and Pituello, 2017; Takahashi, et al, 1995). Multiple molecular mechanisms link G1 phase length and choice between proliferation and differentiation in multiple stem cell types, including various pluripotent stem cells (Julian, et al, 2016; Dalton, 2015) and neural stem cells (Liu, et al, 2019).…”