The stromal cell population in bone marrow has been the focus of much attention since it has been shown that this cell population can be expanded and differentiated into cells with the phenotype of bone, cartilage, muscle, stroma, neural, and fat cells. We evaluated umbilical cord blood (UCB) for the presence of these cells. From the mononuclear fraction of UCB, we demonstrated the presence of a subset of cells that have been maintained in continuous culture for more than 6 months (>10 passages). These adherent cell populations express adhesion molecules CD13+, CD29+, and CD44+, but not antigens of hematopoietic differentiation. Exposure of these cells to osteogenic agents resulted in an increase in expression of alkaline phosphatase and the appearance of hydroxyapatite nodules by Von Kossa staining. Incubation with adipogenic agents resulted in morphological change and staining with Oil Red O. In addition, when exposed to basic fibroblast growth factor and human epidermal growth factor the cells underwent changes consistent with cells of neural origin. These changes were demonstrated by a combination of immunofluorescent labeling and Western immunoblots for neural-specific markers. Thus, similar to what has been previously reported with bone marrow, cord blood contains a population of cells that can be expanded in culture and are able to express the phenotype of multiple lineages. Cord blood multilineage cells are slower to establish in culture, have a lower precursor frequency and a lower level of bone antigen expression, and lack constitutive expression of neural antigens when compared to bone marrow, suggesting a more primitive population. Cord blood may prove to be a new source of cells for cellular therapeutics for stromal, bone, and, potentially, neural repair.

The distinct axonal tracts of the mature nervous system are defined during development by sets of substrate-bound and diffusible molecular signals that promote or restrict axonal elongation. In the adult cerebral cortex, efferent and afferent axons are segregated within the white matter. To define the relationship of growing efferent and afferent axons in the developing murine cortex to chondroitin sulfate proteoglycans (CSPGs) in the pericellular and extracellular matrix, we used the fluorescent tracer Dil to determine axonal trajectories and immunolabeling to disclose the distribution of CSPGs. Axons of neurons in the preplate are the first to leave the cortex; they arise in the CSPG-rich preplate and extend obliquely across it to enter the CSPG-poor intermediate zone. Slightly later, axons of cortical plate neurons extend directly across the CSPG-rich subplate, and then turn abruptly to run in the upper intermediate zone. In contrast, once afferent axons from the thalamus reach the developing cortical wall, their intracortical trajectory is centered on the CSPG-rich subplate, above the path taken by efferent axons. Our findings demonstrate a molecular difference between the adjacent but distinct efferent and afferent pathways in developing neocortex. Early efferents cross the subplate and follow a pathway that contains very little CSPG, while afferents preferentially travel more superficially within the CSPG-rich subplate. Thus, CSPGs and associated extracellular matrix (ECM) components in the preplate/subplate do not form a barrier to axonal initiation or outgrowth in the neocortex as they may in other locations. Instead, their distribution suggests a role in defining discrete axonal pathways during early cortical development.

Obesity is associated with headache frequency and disability in the pediatric headache population. For children who are overweight, weight loss can contribute to a reduction in headaches over time. Clinicians should consider child weight status in providing care for pediatric headache.

The first thalamocortical axons to arrive in the developing cerebral cortex traverse a pathway that is separate from the adjacent intracortical pathway for early efferents, suggesting that different molecular signals guide their growth. We previously demonstrated that the intracortical pathway for thalamic axons is centered on the subplate (Bicknese et al. [1994] J. Neurosci. 14:3500-3510), which is rich in chondroitin sulfate proteoglycans (CSPGs; Sheppard et al. [1991] J. Neurosci. 11:3928-3942), whereas efferent axons cross the subplate to exit in a zone containing much less CSPG. To define the molecular composition of the subplate further, we used antibodies against CSPG core proteins and chondroitin sulfate disaccharides in an immunohistochemical analysis of their distribution in the developing neocortex of the rat. Immunolabeling for neurocan, a central nervous system-specific CSPG (Rauch et al. [1992] J. Biol. Chem. 267:19537-19547), and for chondroitin 6-sulfate and unsulfated chondroitin becomes prominent in the subplate before the arrival of thalamic afferents. Immunolabeling is initially sparse in the cortical plate but appears later in maturing cortical layers. A postnatal decline in immunolabeling occurs uniformly for most proteoglycans, but, in the somatosensory cortex, labeling for neurocan, phosphacan, and chondroitin 4- and 6-sulfate declines in the centers of the whisker barrels before the walls. In contrast to neurocan, immunolabeling for other proteoglycans is either uniformly distributed (syndecan-1, N-syndecan, 5F3, phosphacan, chondroitin 4-sulfate), restricted to axons (PGM1), distributed exclusively on nonneuronal elements (2D6, NG2, and CD44), or undetectable (9.2.27, aggrecan, decorin). Thus, neurocan is a candidate molecule for delineating the intracortical pathway of thalamocortical axons and distinguishing it from that of cortical efferents.