Connecting thalamus and cortex: The role of ephrins

Abstract

The complex task of wiring up the brain during embryonic development is achieved by a multitude of guidance signals acting in complex combinations to drive growing axons to their proper targets. The somatosensory system provides an extensively studied model system featuring many universal mechanisms of neural development. In rodents, it constitutes an important model to study how precise topographic connections are achieved. Recent evidence suggests that the Eph/ephrin family of guidance molecules is of pivotal importance for the development of the somatosensory system. Members of Eph/ephrin family are thought to be involved in the global presorting of thalamic axons projecting to the cortex, in labeling specific cortical areas for innervation, in providing topographic cues within the target area, and in distinguishing cortical layers for intracortical wiring. The Eph/ephrin system also seems to contribute to the formation of specific corticothalamic feedback projections. So far, the functions of only a few members of the Eph/ephrin family have been examined, but expression analysis indicates complex combinatorial effects of these signaling molecules. Understanding the Eph/ephrin wiring code is expected to yield new insights into the development and plasticity of brain circuits involved in higher functions.

Postnatal Generation of Neurons in the Ventrobasal Nucleus of the Rat Thalamus

“…On the other hand, this generation coincides with the establishment of the descending corticothalamic projection (Jones, 1997;Uziel et al, 2006). This notion is supported by evidence that (1) layer VI, the source of most corticothalamic projections, has a considerable number of neurotrophin-expressing neurons Miller, 1995, 2000) and (2) the thalamus does not have neurons capable of manufacturing a neurotrophin(s) (Baquet et al, 2004), but it does have cells that express neurotrophin receptors (Vitalis et al, 2002;present study).…”

EphrinA5 protein distribution in the developing mouse brain

“…Feldheim et al [10] described ephrinA5 mRNA expression from E14.5, in the dorsal and ventral lateral geniculate nuclei in a ventral, lateral and anterior (high) to dorsal, medial and posterior (low) gradient. Between E16.5 and E18.5, nuclei of the lateral part of the dorsal thalamus [27] and ventral nuclei [29] both exhibit ephrinA5 mRNA. Our results partially match with these previous studies, as we showed here that ephrinA5 protein was strongly expressed in the thalamus in a ventral and rostral (high) to dorsal and caudal (low) gradient especially from E12.5 to E16.5.…”

“…In the telencephalon, ephrinA5 mRNA is expressed in the olfactory system [17,18], in the lateral and medial ganglionic eminences and their ventricular zones [19-21] and in the cortex [22-27]. EphrinA5 transcript expression has been also detected in the diencephalon (hypothalamus and thalamus) [10,21,27-29] and in the inferior and superior colliculi as well as in the pretectal nuclei and the red nucleus of the mesencephalon [28,30,10,21]. …”

“…In several systems such as the retinotectal [10,30], the retinothalamic [31] and the thalamocortical [23,24,26,29] ones, ephrinA5 and its receptors have been found to be expressed in opposite gradients on the projections and their target respectively, leading to a repulsive ligand-receptor interaction. An exception to these observations was described in the olfactory system, where high ephrinA5 expressing region is connected by axons containing an important concentration of ephrinA5 receptors.…”

Development of axonal pathways in the human fetal fronto‐limbic brain: histochemical characterization and diffusion tensor imaging

“…The essential component of the subplate zone is the extracellular matrix, which builds up to 70% of the neuropil . The extracellular matrix of the subplate contains different attractant and repellent molecules, such as fibronectin (Chun & Shatz, 1988;Tuttle et al 1995;Pearlman & Sheppard, 1996), semaphorins, ephrins and other molecules (Hoerder-Suabedissen et al 2009; for reviews see Judaš et al 2003;Uziel et al 2006). The possible cellular sources of the extracellular matrix and axonal guidance molecules are subplate cells (neurons or glia).…”