Biomedical subjects

J G Whitesides

Publications and source records attributed to J G Whitesides.

3 recordsLinked to original sources

PubMed1998

p59fyn and pp60c-src modulate axonal guidance in the developing mouse olfactory pathway.

The Src-family tyrosine kinases p59fyn and pp60c-src are localized on axons of the mouse olfactory nerve during the initial stages of axonal growth, but their functional roles remain to be defined. To study the role of these kinases, we analyzed the trajectory of the olfactory nerve in E11.5 homozygous null mutant mice lacking single src or fyn gens and double mutants lacking both genes. Primary olfactory axons of single and double mutants exited the olfactory epithelium and projected toward the telencephalon, but displayed differences in fasciculation. The fyn-minus olfactory nerve had significantly more fascicles than than src-minus nerve. Most strikingly, the primary olfactory nerve of src/fyn double mutants showed the greatest degree of defasciculation. These defects, identified by NCAM labeling, were not due to apparent changes in the size of the olfactory epithelium. With the exception of the src-minus mice, which had fever fascicles than the wild type, no obvious differences were observed in coalescence of vomeronasal axons from mutant mice. The mesenchyme of the double and single mutants exhibited only subtle changes in laminin and fibronectin staining, indicating that the adhesive environment of the mesenchyme may contribute in part to defects in fasciculation. The results suggest that signaling pathways mediated by p59fyn and pp60c-src contribute to the appropriate fasciculation of axons in the nascent olfactory system, and comprise partially compensatory mechanisms for axonal adhesion and guidance.

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PubMed1996

Differential adhesion and the initial assembly of the mammalian olfactory nerve.

During the initial assembly of the olfactory pathway, the behavior of olfactory axons changes as they grow from the olfactory epithelium toward the telencephalic vesicle. The axons exit the epithelium singly or in small fascicles, and their growth cones are simple and bullet-shaped. Outside the epithelium, they make a sharp dorsal turn and fasciculate into a single nerve; the growth cones remain simple. Upon entering the ventromedial telencephalon, the axons defasciculate, branch extensively, and end in complex, lamellate growth cones which extend toward the ventrolateral aspect of the telencephalic vesicle. The distribution of laminin, collagen-IV, and fibronectin varies in register with these changes in olfactory axon and growth cone behavior. Each of these extracellular matrix molecules influences olfactory neurite outgrowth and growth cone morphology in vitro consistent with its distribution in vivo. The distribution of E-cadherin, L1, neural cell adhesion molecule (NCAM) and the polysialated form of NCAM also varies in register with changes in olfactory axon behavior. In vitro, L1 modulates embryonic olfactory neurite outgrowth and growth cone morphology consistent with its distribution in vivo. Thus, olfactory axon trajectory, fasciculation, and growth cone morphology change within distinct adhesive environments in the nascent olfactory pathway, and some of the molecules that characterize these environments have differential effects upon olfactory neurite growth and growth cone morphology. Consequently, the patterned expression and activity of extracellular matrix and cell surface adhesion molecules may contribute to the initial assembly of the olfactory pathway.

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PubMed1995

Distinct adhesive behaviors of neurons and neural precursor cells during regional differentiation in the mammalian forebrain.

Prior to the emergence of the major functional subdivisions of the mammalian forebrain--the neocortex, hippocampus, olfactory bulb, basal ganglia, and basal forebrain--the lateral aspect of the telencephalic vesicle is distinguished by early neuronal differentiation assessed by MAP2 and GAP43 expression and increased expression of the Ca(2+)-independent/immunoglobulin superfamily cell adhesion molecules (CAMs) NCAM, L1, and TAG-1. In contrast, the ventral and medial aspects of the vesicle show little early neuronal differentiation and intermediate or undetectable levels of CAM expression. We asked whether cells from these three regions acquire distinct adhesive and recognition properties that reflect their position, state of neuronal differentiation, and level of CAM expression. In a dissociation/reaggregation assay, cells from the lateral telencephalic vesicle form the largest reaggregates while ventral reaggregates are of intermediate size and medial reaggregates are the smallest. This differential adhesion has a Ca(2+)-independent component, and cells in reaggregates from each region maintain expression of CAMs and other neuronal markers consistent with their region of origin. Furthermore, cells from the lateral telencephalon can specifically sort out from medial cells. Little adhesivity is observed prior to early neuronal differentiation and the expression of Ca(2+)-independent CAMs, when the forebrain is still a prosencephalic vesicle, nor does it follow the pattern of detectable CAM expression once forebrain rudiments are formed. Thus, cells in the early developing forebrain acquire distinct adhesive and recognition properties that reflect the concurrent emergence of regional differences in neuronal differentiation and CAM expression. These differences are transient and can only be detected in the telencephalic vesicle before and during the morphogenesis of rudiments of major forebrain subdivisions.

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