Thalamocortical development: how are we going to get there?

• Published in: Nature reviews. Neuroscience Vol. 4; no. 4; pp. 276 - 289
• Main Authors: López-Bendito, Guillermina, Molnár, Zoltán
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2003; Nature Publishing Group
• Subjects: Animal Genetics and Genomics; Animals; Behavioral Sciences; Biological and medical sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Body Patterning - genetics; Cell Communication - genetics; Cell Differentiation - genetics; Cerebral Cortex - cytology; Cerebral Cortex - embryology; Cerebral Cortex - metabolism; Epigenetics; Fundamental and applied biological sciences. Psychology; Gene expression; General aspects. Models. Methods; Growth Cones - metabolism; Growth Cones - ultrastructure; Growth Substances - genetics; Growth Substances - metabolism; Mice; Neural Pathways - cytology; Neural Pathways - embryology; Neural Pathways - metabolism; Neurobiology; Neurons; Neurosciences; review-article; Specialization; Thalamus - cytology; Thalamus - embryology; Thalamus - metabolism; Vertebrates: nervous system and sense organs; Cerebral cortex; Central nervous system; Development; Thalamus; Review; Anatomy; Gene expression; Encephalon
• ISSN: 1471-003X; 1471-0048; 1471-0048; 1469-3178
• DOI: 10.1038/nrn1075

Key Points The mechanisms that control neocortical regionalization have been the subject of much debate. Intrinsic mechanisms, such as differential gene expression that is autonomous to the neocortex, and extrinsic influences, such as input from thalamocortical afferents, have both gained support from recent studies. Most neocortical neurons, including the projection neurons, are generated within the ventricular and subventricular zones of the lateral ventricle. The first postmitotic neurons accumulate below the pial surface, and later-born neurons migrate along radial glial processes to form the cortical plate. The thalamus and cortex develop synchronously — virtually all the thalamic neurons in the rat are born between embryonic day (E) 13 and E19, which coincides with the period of neuron generation in the cortex. The dorsal thalamic neurons send projections to the cortex. Thalamocortical and corticothalamic projections have to cross several emerging boundary zones, including the diencephalic–telencephalic and pallial–subpallial boundaries, to reach their ultimate target cells. Their fibre trajectories and fasciculation patterns change as they cross these sharp gene expression boundaries. Attractive and repulsive factors, and axon guidance molecules from the cortex are believed to have an important role in channelling thalamocortical projections through the forebrain. These factors include limbic-associated membrane proteins (LAMP), the orphan nuclear receptor Coup-tfi, Cadherin (Cdh) 6, Cdh8, Cdh11, ephrins and Eph receptors. The 'handshake hypothesis' postulates that projections from the thalamus and the cortical preplate cells meet and intermingle in the basal telencephalon, such that thalamic axons grow over a scaffold of preplate axons. Errors in both corticothalamic and thalamocortical pathfinding have been described in mice with mutations in transcription factor genes that are expressed in the cortex ( Tbr1 ), thalamus ( Gbx2 ) or in both ( Pax6 ). Thalamic fibres arrive at the appropriate cortical regions before their ultimate target neurons are born, and they have to wait for two or three days before they can establish their final innervation pattern within the cortical plate. It has been proposed that while the thalamic axons accumulate in the subplate, they engage in activity-dependent interactions with the sensory periphery, and this might lead to their realignment before they enter the cortex. Although some aspects of early cortical regionalization do not seem to require extrinsic influences, there is considerable evidence that the differentiation of many of the anatomical features that distinguish different cortical areas depends to a large extent on the input of thalamocortical axons. Peripheral neurons are already generating spontaneous activity patterns by the time that sensory afferents begin to reach the thalamus, and these activity patterns could influence the formation of thalamocortical terminals within the subplate and layer IV of the cortex. The arealization of the mammalian cortex is believed to be controlled by a combination of intrinsic factors that are expressed in the cortex, and external signals, some of which are mediated through thalamic input. Recent studies on transgenic mice have identified families of molecules that are involved in thalamic axon growth, pathfinding and cortical target selection, and we are beginning to understand how thalamic projections impose cytoarchitectonic differentiation on the developing cortex. By unravelling these mechanisms further, we should be able to increase our understanding of the principles of cortical organization.