Specific beta1 integrins mediate adhesion, migration, and differentiation of neural progenitors derived from the embryonic striatum.
Early inductive signals within the embryonic mammalian forebrain establish two major germinal regions along the dorsal-ventral axis. The dorsal germinal zone eventually forms the cerebral cortex while the ventral ganglionic eminence primarily forms the striatum and globus pallidus. The mechanisms leading to patterning of specific forebrain structures from these distinct germinal regions are not fully understood but may involve the adhesive and migratory properties of regionally specified cells and their interactions with the extracellular environments in which they reside. In the present study, we isolated ganglionic eminence neural progenitor cells (geNPC), precursors of the adult striatum, from the ventral forebrain germinal zone and analyzed adhesion, migration, and differentiation of geNPC on various extracellular matrix (ECM) substrates in vitro. Specifically, we evaluated the role of beta1 integrins, a family of cell surface receptors important in neural development, in mediating geNPC behavior on ECM molecules expressed in embryonic brain tissue. Adhesion and migration of geNPC were significantly enhanced on laminin (LN) and fibronectin (FN) relative to other ECM substrates. Antibody perturbation experiments revealed that although geNPC express several beta1 integrins (alpha1beta1, alpha2beta1, alpha3beta1, alpha5beta1, alpha6beta1, alphavbeta1), adhesion and migration on LN and FN were primarily mediated by alpha6beta1 and alpha5beta1, respectively, and these interactions were confirmed by biochemical cross-link/extraction procedures. Finally, neuronal differentiation of geNPC was enhanced on LN, indicating a role for LN in geNPC differentiation. beta1 integrin-ECM interactions may contribute to basic mechanisms of striatal development and may explain the potent migratory capacity of geNPC transplanted into the adult brain.
Tate
Matthew C
MC
Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332-0535, USA.
García
Andrés J
AJ
Keselowsky
Benjamin G
BG
Schumm
Michael A
MA
Archer
David R
DR
LaPlaca
Michelle C
MC
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D039081:Integrin alpha5beta1 / Q000378:metabolism; D039121:Integrin alpha6beta1 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018874:Spheroids, Cellular; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000906:Antibodies; D005353:Fibronectins; D039081:Integrin alpha5beta1; D039121:Integrin alpha6beta1; D019012:Integrin beta1; D007797:Laminin