RESUMO
The oligodendrocyte myelin glycoprotein is a glycosylphosphatidylinositol-anchored protein expressed by neurons and oligodendrocytes in the central nervous system. Attempts have been made to identify the functions of the myelin-associated inhibitory proteins (MAIPs) after axonal lesion or in neurodegeneration. However, the developmental roles of some of these proteins and their receptors remain elusive. Recent studies indicate that NgR1 and the recently discovered receptor PirB restrict cortical synaptic plasticity. However, the putative factors that trigger these effects are unknown. Because Nogo-A is mostly associated with the endoplasmic reticulum and myelin associated glycoprotein appears late during development, the putative participation of OMgp should be considered. Here, we examine the pattern of development of OMgp immunoreactive elements during mouse telencephalic development. OMgp immunoreactivity in the developing cortex follows the establishment of the thalamo-cortical barrel field. At the cellular level, we located OMgp neuronal membranes in dendrites and axons as well as in brain synaptosome fractions and axon varicosities. Lastly, the analysis of the barrel field in OMgp-deficient mice revealed that although thalamo-cortical connections were formed, their targeting in layer IV was altered, and numerous axons ectopically invaded layers II-III. Our data support the idea that early expressed MAIPs play an active role during development and point to OMgp participating in thalamo-cortical connections.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento/genética , Glicoproteína Associada a Mielina/biossíntese , Glicoproteína Associada a Mielina/genética , Telencéfalo/metabolismo , Animais , Mapeamento Encefálico , Diferenciação Celular/genética , Córtex Cerebral/citologia , Córtex Cerebral/embriologia , Córtex Cerebral/metabolismo , Proteínas Ligadas por GPI , Cones de Crescimento/metabolismo , Células HEK293 , Humanos , Camundongos , Camundongos Knockout , Proteínas da Mielina , Glicoproteína Associada a Mielina/deficiência , Glicoproteína Mielina-Oligodendrócito , Fibras Nervosas Mielinizadas/metabolismo , Vias Neurais/embriologia , Vias Neurais/crescimento & desenvolvimento , Vias Neurais/metabolismo , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/citologia , Córtex Somatossensorial/embriologia , Córtex Somatossensorial/metabolismo , Telencéfalo/citologia , Telencéfalo/embriologia , Tálamo/citologia , Tálamo/embriologia , Tálamo/metabolismoRESUMO
Anosmin-1 participates in the development of the olfactory and GnRH systems. Defects in this protein are responsible for both the anosmia and the hypogonadotrophic hypogonadism found in Kallmann's syndrome patients. Sporadically, these patients also manifest some neurological symptoms that are not explained in terms of the developmental defects in the olfactory system. We describe the pattern of Anosmin-1 expression in the central nervous system during rat development using a novel antibody raised against Anosmin-1 (Anos1). The areas with Anos1-stained neurons and glial cells were classified into three groups: (1) areas with immunoreactivity from embryonic day 16 to postnatal day (P) 15; (2) areas with Anosmin-1 expression only at postnatal development; (3) nuclei with immunoreactivity only at P15. Our data show that Anos1 immunoreactivity is detected in projecting neurons and interneurons within areas of the brain that may be affected in patients with Kallmann's syndrome that develop both the principal as well as sporadic symptoms.