How the extracellular matrix shapes neural development

Abstract

During development, both cells and tissues must acquire the correct shape to allow their proper function. This is especially relevant in the nervous system, where the shape of individual cell processes, such as the axons and dendrites, and the shape of entire tissues, such as the folding of the neocortex, are highly specialized. While many aspects of neural development have been uncovered, there are still several open questions concerning the mechanisms governing cell and tissue shape. In this review, we discuss the role of the extracellular matrix (ECM) in these processes. In particular, we consider how the ECM regulates cell shape, proliferation, differentiation and migration, and more recent work highlighting a key role of ECM in the morphogenesis of neural tissues.

Keywords: development; extracellular matrix; tissue shape.

Figure 1.

ECM, integrins and progenitor cell behaviour. (a) Images showing E14.5 mouse neocortex after 24 h of whole hemisphere (HERO) culture with either control IgG antibody (left panels) or the integrin αvβ3 activating antibody, LIBS-6 (right panels), with DAPI staining (blue, upper panels) and immunofluorescence for the mitotic marker PH3 (white, lower panels). White dashed lines delineate the ventricular zone (VZ) and subventricular zone (SVZ) boundary. Scale bar represents 50 µm. Adapted from [64]. (b,c) Quantification of PH3 positive (mitotic) cells in the (b) VZ (APs) and (c) SVZ (BPs). Adapted from [64]. (d) Images showing GFP in the neocortex of E11 wild-type (left) and Itgb1^flox/flox (knockout) (right) mice that were electroporated with CRE-IRES-eGFP and analysed after 24 h. White dashed lines delineate the basal surface. White arrowheads delineate detached radial glia processes. Scale bar represents 100 µm. Adapted from [65]. (e) Schematic summarizing the effects of blocking, knocking out or activating ECM and integrins on neuroepithelial and radial glial cell behaviour.

Figure 2.

ECM and cell migration. (a) Images showing INM of GFP expressing neuroepithelial cells in the neural tube of the 9–10 somite stage wild-type (top panels) or tab mutant (lower panels) zebrafish. White dashed lines delineate the path travelled by the centre of the nucleus. Purple arrows indicate the nuclear division. Note the apical division of the nucleus in the wild-type, but the more basal division in the tab mutant. Scale bar represents 10 µm. Adapted from [87]. (b,c) Coronal sections of the neocortex of newborn P0 wild-type (b,b′) or laminin gamma 1 mutant (c,c′) mice. White boxes delineate areas shown in b′ and c′. Red arrows indicate the marginal zone in the wild-type (b′) and abnormal organisation in the laminin gamma 1 mutant (c,c′). Scale bars represent 500 µm (b,c) and 50 µm (b′,c′). Adapted from [77]. (d) Schematic summarizing the effects of ECM on neural progenitor and neuronal migration.

Figure 3.

ECM and morphogenesis. (a) Images showing the ventral view of the CNS of late-third instar Drosophila larvae from the wild-type (left panel) and runaway mutant (right panel), with DAPI staining (blue), immunofluorescence for the neuronal marker ELAV (green) and axonal marker HRP (red). White dashed lines delineate the neuronal structures, which are also marked by white asterisks. Arrows indicate loss of neurons, arrowhead indicates small neuronal cluster. Scale bar represents 100 µm. Adapted from [23]. (b) Images showing 13 gestation week (GW) human fetal neocortex after 24 h of culture in control (upper panels) or after the addition of ECM components HAPLN1, lumican and collagen I, which induce folding of the cortical plate (lower panels), with DAPI staining (blue) and immunofluorescence for the radial glial process marker nestin (grey). White dashed boxes delineate areas shown in the panels on the right. Scale bar represents 50 µm. Adapted from [24]. (c) Schematic summarizing the effects of ECM on neural morphogenesis at the cellular and tissue levels.