A Critical Function of the Pial Basement Membrane in Cortical Histogenesis

Abstract

Mice with a targeted deletion of the nidogen-binding site of laminin gamma1 were used to study the function of the pial basement membrane in cortical histogenesis. The pial basement membrane in the mutant embryos assembled but was unstable and disintegrated at random segments. In segments with a disrupted basement membrane, radial glia cells were retracted from the pial surface, and radially migrating neurons, including Cajal-Retzius cells and cortical plate neurons, passed the meninges or terminated their migration prematurely. By correlating the disruptions in the pial basal lamina with changes in the morphology of radial glia cells, the aberrant migration of Cajal-Retzius cells, and subsequent dysplasia of cortical plate neurons, the present data establish a causal relationship of proper cortical histogenesis with the presence of an intact pial basement membrane.

The microenvironment of the embryonic neural stem cell: Lessons from adult niches?

“…However, just as in the ␣6 Ϫ/Ϫ mice, there is no morphological abnormality in the VZ (GrausPorta et al, 2001). As similar abnormalities of pial discontinuities and cortical ectopias are seen in the mice with deletion of the laminin ␥1 chain (so preventing laminin trimer formation) (Halfter et al, 2002), we can conclude that the interaction between the stem cell basal end foot and the pia is important for neuronal migration, as expected given that these cells use the basal process as a guidepost for migration (Rakic, 1995). However, the lack of a VZ abnormality is surprising given the levels of integrin expression in this region and recent evidence in ES cells showing that laminin 111 (comprising the ␣1, ␤1, and ␥1 chains) can efficiently facilitate transition of cells into neuronal precursors and neurons (Goetz et al, 2006), further suggesting a role for the integrin/extracellular matrix interaction in mediating cell proliferation and fate choices.…”

“…Loss of apical adhesion could result in displacement of the NSC into deeper cortical layers, generating a random distribution of cells (NSCs, basal progenitors, and differentiated cells) in the cortex and a possible increase in the number of intermediate progenitors and differentiated cells as seen in Rho-GTPase cdc42 mutants (Cappello et al, 2006) and aPKC (Imai et al, 2006). In contrast, loss of basal adhesion could result in migration defects leading to ectopias in the cortex as seen in mice deficient in laminin ␥1 (Halfter et al, 2002), ␣6 integrin (Georges-Labouesse et al, 1998;Haubst et al, 2006), and ␤1 integrin (Graus-Porta et al, 2001). Finally, loss of VZ growth control may be a stem cell tumor-initiating step and could, if present throughout the cortex, result in an increase in NSC numbers and brain size as seen in mice deficient for the tumor suppressor PTEN (Groszer et al, 2001).…”

Postnatal Development of the Central Nervous System: Anomalies in the Formation of Cerebellum Fissures

“…glial cells lost their footing to the pial surface and retracted wherever the pial basement membrane was ruptured (Halfter et al, 2002;Zerbalis et al, 2007).…”

SPARC is expressed by macroglia and microglia in the developing and mature nervous system

“…Radial glial endfeet provide anchorage at the meningeal basement membrane of the pia mater to support the highly extended morphology of radial fibres in the developing brain. Disruption of this attachment causes defects in cortical lamination, such as in mice with genetic defects in integrins, ILK, FAK, and ECM components (Graus-Porta et al, 2001;Halfter et al, 2002;Beggs et al, 2003;Poschl et al, 2004;Niewmierzycka et al, 2005). SPARC could potentially act to anchor radial glial endfeet, either by modulating the stability of focal adhesions via integrin-mediated FAK and ILK signaling (Shi et al, 2007), or alternatively by the assembly and maintenance of ECM components in the basement membrane (Yan et al, 2003).…”