REGULATION OF THALAMIC NEURITE OUTGROWTH BY THE EPH LIGAND EPHRIN-A5 - IMPLICATIONS IN THE DEVELOPMENT OF THALAMOCORTICAL PROJECTIONS

GAO PP YUE Y ZHANG JH CERRETTI DP LEVITT P ZHOU RP

Pp. Gao et al., REGULATION OF THALAMIC NEURITE OUTGROWTH BY THE EPH LIGAND EPHRIN-A5 - IMPLICATIONS IN THE DEVELOPMENT OF THALAMOCORTICAL PROJECTIONS, Proceedings of the National Academy of Sciences of the United Statesof America, 95(9), 1998, pp. 5329-5334

42

INGLESE

Article

Multidisciplinary Sciences

Proceedings of the National Academy of Sciences of the United Statesof America → ACNP

0027-8424

95

9

1998

5329 - 5334

ISI

0027-8424(1998)95:9<5329:ROTNOB>2.0.ZU;2-1

The cerebral cortex is parcellated into different functional domains t hat receive distinct inputs from other cortical and subcortical region s. The molecular mechanisms underlying the specificity of connections of cortical afferents remain unclear. We report here that the Eph fami ly tyrosine kinase receptor EphA5 and the ligand ephrin-A5 may play a key role in the exclusion of the limbic thalamic afferents from the se nsorimotor cortex by mediating repulsive interactions. In situ hybridi zation shows that the EphA5 transcript is expressed at high levels in both cortical and subcortical limbic regions, including the frontal co rtex, the subiculum, and the medial thalamic nuclei. In contrast, ephr in-A5 is transcribed abundantly in the sensorimotor cortex. Consistent with the complementary expression, the ligand inhibited dramatically the growth of neurites from neurons isolated from the medial thalamus but was permissive for the growth of neurites from lateral thalamic ne urons, which is primarily nonlimbic, Similarly, the growth of neurites from Eph-A5-expressing neurons isolated from the subiculum was inhibi ted by ephrin-A5. Our studies suggest that the Eph family ligand ephri n-A5 serves as a general inhibitor of axonal growth from limbic neuron s, which may serve to prevent innervation of inappropriate primary sen sorimotor regions, thus contributing to the generation of specificity of thalamic cortical afferents.