Structure and modulation of neural cell adhesion molecules in early and late embryogenesis.
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Biomedical subjects
Publications and source records attributed to C M Chuong.
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Previous studies in this laboratory have led to the identification and purification of a chicken cell surface protein named "neural cell adhesion molecule" (N-CAM) that is involved in neural cell-cell and neurite-neurite interactions. In the present investigation, we have found that a similar molecule exists in the mouse and have confirmed that it is also present in rat neural tissue. A monoclonal antibody to chicken N-CAM that crossreacted with mouse and rat brains and an independently derived monoclonal antibody to mouse N-CAM were used to purify an antigen from perinatal mouse and rat brains. The purified neural antigen resembles chicken N-CAM in its ability to neutralize antibodies that inhibit neural cell aggregation and also in its biochemical properties including molecular weight, sialic acid content, amino acid composition, and autoconversion to a smaller polypeptide. Like chicken N-CAM, the murine molecule is found throughout the nervous system and over the entire neuronal cell surface. These results strongly suggest that the molecule is evolutionarily related to chicken N-CAM and prompt the hypothesis that cell adhesion involving N-CAM is a fundamental mechanism existing in nervous systems of different phylogenetic classes of animals.
The neural cell adhesion molecule (N-CAM) has an unusually high amount of sialic acid (28-35 g/100 g of polypeptide) and shows microheterogeneity in electrophoretic gels in its embryonic or E form. During development, the molecule undergoes conversion to several adult or A forms, which resemble the E form but which on the average have only 10% sialic acid and do not appear to be microheterogeneous. In the present study, rabbit antibodies to mouse N-CAM and two different monoclonal antibodies were used to follow the E leads to A conversion in normal and mutant mice. E leads to A conversion to three forms (Mr 180,000, Mr 140,000, and Mr 120,000) was found to occur at different rates in different parts of the brains of wild-type mice. Examination of the entire cerebellum of the granuloprival mouse mutant staggerer (sg/sg) showed that the E leads to A conversion did not occur by 21 days after birth, whereas in wild type it was almost complete at that time. There was also some delay in E leads to A conversion within the cerebral cortex of sg/sg, although phenotypically no evidence of cortical disorder has been detected. In pooled tissues from phenotypically normal-appearing littermates, (i.e., a mixture of sg/+ and +/+), a slight conversion delay was also found in cerebellum and cortex. The mutants weaver, reeler, and jimpy all showed normal schedules of E leads to A conversion. These observations raise the possibility that a major defect in staggerer mutants relates to a failure in local surface modulation of N-CAM to produce the A forms of the molecule. Some of the failures of synapse formation and of cell survival seen in this disease may result from the anomaly, which is likely to alter the binding properties of N-CAM at critical times of development.
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The integument forms the interface between animals and the environment. During evolution, diverse integument and integument appendages have evolved to adapt animals to different niches. The formation of these different integument forms is based on the acquisition of novel developmental mechanisms. This is the way Nature does her tissue/organ engineering and experiments. To do tissue engineering of the integument in the new century for medical applications, we need to learn more principles from developmental and evolutionary studies. A novel diagram showing the evolution and development of integument complexity is presented, and the molecular pathways involved discussed. We then discuss two examples in which the gain and loss of appendages are modulated: transformation of avian scale epidermis into feathers with mutated beta catenin, and induction of chicken tooth like appendages with FGF, BMP and feather mesenchyme.