Highlights d Basal progenitors (BPs) in the human neocortex have six distinct morphotypes d Increasing BP proliferative capacity is correlated with increasing BP process numbers d Membrane-bound PALMD is required for and sufficient to increase BP processes d Induction of BP processes by PALMD promotes BP proliferation via integrin signaling
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.
Neocortical expansion, thought to underlie the cognitive traits unique to humans, is accompanied by cortical folding. This folding starts around gestational week (GW) 20, but what causes it remains largely unknown. Extracellular matrix (ECM) has been previously implicated in neocortical expansion and here we investigate the potential role of ECM in the formation of neocortical folds. We focus on three specific ECM components localized in the human fetal cortical plate (CP): hyaluronan and proteoglycan link protein 1 (HAPLN1), lumican and collagen I (collectively, HLC). Addition of HLC to cultures of human fetal neocortex (11-22 GW) caused local changes in tissue stiffness, induced CP folding, increased CP hyaluronic acid (HA), and required the HA-receptor CD168 and downstream ERK signaling. Importantly, loss of HA reduced HLC-induced and 22 GW physiological nascent folds. This was altered in samples with neurodevelopmental disorders, indicating it may be a useful system to study such disorders.
SummaryThe expression of adhesion molecules by stem cells within their niches is well described, but what is their function? A conventional view is that these adhesion molecules simply retain stem cells in the niche and thereby maintain its architecture and shape. Here, we review recent literature showing that this is but one of their roles, and that they have essential functions in all aspects of the stem cellniche interaction -retention, division and exit. We also highlight from this literature evidence supporting a simple model whereby the regulation of centrosome positioning and spindle angle is regulated by both cadherins and integrins, and the differential activity of these two adhesion molecules enables the fundamental stem cell property of switching between asymmetrical and symmetrical divisions.Key words: Cadherin, Integrin, Adherens junction, Basal lamina, Centrosome, Stem cell niche Journal of Cell Sciencedirectly for follicle stem cells in the Drosophila ovary, where cells that lack the -integrin subunit PS were frequently mislocalised into the centre of the gonad, away from their normal location on the basal lamina at the edge (O'Reilly et al., 2008) (Fig. 1D). Interestingly, these stem cells also produce laminins, and laminins constitute one of the integrin ligands in the underlying basal lamina. This, therefore, provides an example of stem cells generating the signals required for their own maintenance within the niche.In adult mammalian niches, the role for adhesion molecules in retaining the correct position of stem cells remains unproven. In the bone marrow niche of haematopoietic stem cells (HSCs), a population of HSCs is located adjacent to the endosteum, the cell layer on the bone surface (Kiel et al., 2005;Zhang et al., 2003). It has been proposed that the HSCs are anchored to a subpopulation of osteoblasts at this site by N-cadherin, with these osteoblasts providing a niche environment (Zhang et al., 2003) -a situation analogous to that in Drosophila stromal gonadal niches. However, studies that used the signalling lymphocyte activating molecule (SLAM) family of lymphocyte receptors as markers of HSCs revealed that only a minority of HSCs is found adjacent to the endosteum; by contrast, the majority was found to be associated with the sinusoidal endothelial cells within the bone (Kiel et al., 2005). Furthermore, mice with greatly reduced numbers of osteoblasts have no alterations in HSC numbers (Kiel et al., 2007), and the conditional deletion of N-cadherin from HSCs has no effect on haematopoiesis (Kiel et al., 2009). Together, these observations cast doubt on the concept of an N-cadherin-dependent osteoblastic niche as being required for haematopoiesis. With respect to integrins, it has been reported that epithelial stem cells in several tissues, including the skin and brain, express high levels of 6 and/or 1 integrins (which heterodimerise to generate a laminin receptor) (Hall et al., 2006; Jones and Watt, 1993). Equally, laminins that contact the stem cells are present in the under...
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