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Publisher Summary In this chapter, three model systems have been described that exemplify the presence and potential biological functions of boundary extracellular matrix (ECM) molecules. Even though these developmentally regulated proteins, sometimes referred to as recognition molecules, are often uniformly expressed in low-levels throughout the developing neuraxis, their dense concentration in so-called boundary regions alerted to their possible functions as interfaces between different brain structures or units. This cordone hypothesis is also consistent with the observed upregulation of boundary molecules in association with the glial scar, and bioassays of such molecules in the astroglial scar reveal their complex interactions with numerous other molecules that can both encourage or deter neuronal adhesion and neurite growth. The persistent expression of boundary ECM molecules in the neurogenic subependymal zone (SEZ) may prove to be the most insightful model for studying the many roles of these molecules. Because cells are born, migrate, and die in relation to an enhanced ECM expression in vivo in the rostral migratory stream, as well as the inferred role of ECM in the generation of novel proliferative spheres in vitro, future studies need to focus on the patterns of gene expression of SEZ-derived stem and precursor cells in relation to ECM expression in order to establish their roles during the proliferation and specification of neurons and glia.

From all of the studies of developmentally regulated molecules as well as the impressive proliferation of cells within the SEZ, we would like to propose that the SEZ of the adult brain, from the lateral ventricles of the cerebrum to the central canal of the spinal cord, represents a potential "brain marrow" from which stem and progenitor cells can be further studied and exploited for cell replacement and circuitry repair paradigms for neurological disease. Without question the SEZ is not as regenerative or pleuripotential as bone marrow or other hematopoietic systems, but there are definitely some elements in common. Bone marrow contains a pleuripotent stem cell that under certain conditions (e.g. the presence of certain growth factors and cytokines) gives rise to erythroblasts and myeloblasts whose progeny include erythrocytes, monocytes, thrombocytes and macrophages. Different growth factors can likewise affect the proliferation as well as differentiation of adult CNS stem and progenitor cells, again contributing to diverse cellular phenotypes. The roles for matrix molecules in these events are yet to be discovered, however, there is evidence to suggest that matrix molecules, including tenascin, do interact with hematopoietic stem cells (Yoder and Williams, 1995) to possibly affect their proliferation and differentiation. Future studies might reveal a similar role for the dense ECM expression within the SEZ proliferative/migratory pathway.