Expression profiles of EphA3 at both the RNA and protein level in the developing mammalian forebrain

Kudo, Chikako; Ajioka, Itsuki; Hirata, Yukio; Nakajima, Kazunori

doi:10.1002/cne.20551

Cited by 39 publications

(33 citation statements)

References 32 publications

(26 reference statements)

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“…This suggests that ephrinA5 and its receptors are not expressed in complementary gradient as it has been described for other systems such as the retinotectal one [8,44]. Instead, we showed that ephrinA5 is uniformly expressed in this structure as for its receptors [40-42,35,20]. This ligand-receptor interaction may result in an attraction of the cells, thus regulating the connections of mitral cells.…”

Section: Discussionsupporting

confidence: 69%

“…Indeed, ephrins are known to be involved in cell migration and boundary formation in other nervous systems [2,3], and at this stage the cell body of developing mitral cells appears to transform from tangential to radial orientation with rearrangement of its microtubules structure [39]. Moreover, the presence of potential ephrinA5 receptors such as EphA3 [40], EphB2 [41], EphA5 [35,42,43], EphA7 and EphA4 [35] has been also described in the mitral cells during embryogenesis. This suggests that ephrinA5 and its receptors are not expressed in complementary gradient as it has been described for other systems such as the retinotectal one [8,44].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, we showed a strong ephrinA5 protein expression in other regions of the developing cortex, especially in the parietal, frontal and insular cortices at E16.5, suggesting that ephrinA5 may be involved in the refinement of other thalamocortical projections and probably through an interaction with 3 potential receptors: EphA3, EphA4 and/or EphA5 that have been detected in these regions during mouse embryogenesis. Indeed, EphA3 protein is expressed in the cortical plate and cortical intermediate zone from E12 to P0, especially in thalamocortical axons [40]. EphA4 protein is expressed from E11 to P6 in the developing cortex [56], and EphA5 protein is present in the intermediate zone and cortical plate [43] whereas its transcript is expressed in the dorsal and medial thalamus that connect to the developing cortex [57], suggesting an expression of EphA5 protein in the thalamocortical projections.…”

Section: Discussionmentioning

confidence: 99%

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EphrinA5 protein distribution in the developing mouse brain

Deschamps¹,

Morel²,

Janet³

et al. 2010

BMC Neurosci

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Background EphrinA5 is one of the best-studied members of the Eph-ephrin family of guidance molecules, known to be involved in brain developmental processes. Using in situ hybridization, ephrinA5 mRNA expression has been detected in the retinotectal, the thalamocortical, and the olfactory systems; however, no study focused on the distribution of the protein. Considering that this membrane-anchored molecule may act far from the neuron soma expressing the transcript, it is of a crucial interest to localize ephrinA5 protein to better understand its function. Results Using immunohistochemistry, we found that ephrinA5 protein is highly expressed in the developing mouse brain from E12.5 to E16.5. The olfactory bulb, the cortex, the striatum, the thalamus, and the colliculi showed high intensity of labelling, suggesting its implication in topographic mapping of olfactory, retinocollicular, thalamocortical, corticothalamic and mesostriatal systems. In the olfactory nerve, we found an early ephrinA5 protein expression at E12.5 suggesting its implication in the guidance of primary olfactory neurons into the olfactory bulb. In the thalamus, we detected a dynamic graduated protein expression, suggesting its role in the corticothalamic patterning, whereas ephrinA5 protein expression in the target region of mesencephalic dopaminergic neurones indicated its involvement in the mesostriatal topographic mapping. Following E16.5, the signal faded gradually and was barely detectable at P0, suggesting a main role for ephrinA5 in primary molecular events in topographic map formation. Conclusion Our work shows that ephrinA5 protein is expressed in restrictive regions of the developing mouse brain. This expression pattern points out the potential sites of action of this molecule in the olfactory, retinotectal, thalamocortical, corticothalamic and mesostriatal systems, during development. This study is essential to better understand the role of ephrinA5 during developmental topographic mapping of connections and to further characterise the mechanisms involved in pathway restoration following cell transplantation in the damaged brain.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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EphrinA5 protein distribution in the developing mouse brain

Deschamps¹,

Morel²,

Janet³

et al. 2010

BMC Neurosci

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“…7A,C; supplementary material Fig. S7A,C,E,G,I,K,M,O; Kudo et al, 2005). In the age-matched Olig2-KO forebrain, the Epha3-and Epha5-expressing TE was dorsally expanded and, conversely, the Ephas-negative prethalamus were reduced in size ( Fig.…”

Section: Disorganized Tcas Extend From Non-olig2 Lineage Cellsmentioning

confidence: 92%

Development of the prethalamus is crucial for thalamocortical projection formation and is regulated by Olig2

et al. 2014

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Thalamocortical axons (TCAs) pass through the prethalamus in the first step of their neural circuit formation. Although it has been supposed that the prethalamus is an intermediate target for thalamocortical projection formation, much less is known about the molecular mechanisms of this targeting. Here, we demonstrated the functional implications of the prethalamus in the formation of this neural circuit. We show that Olig2 transcription factor, which is expressed in the ventricular zone (VZ) of prosomere 3, regulates prethalamus formation, and loss of Olig2 results in reduced prethalamus size in early development, which is accompanied by expansion of the thalamic eminence (TE). Extension of TCAs is disorganized in the Olig2-KO dorsal thalamus, and initial elongation of TCAs is retarded in the Olig2-KO forebrain. Microarray analysis demonstrated upregulation of several axon guidance molecules, including Epha3 and Epha5, in the Olig2-KO basal forebrain. In situ hybridization showed that the prethalamus in the wild type excluded the expression of Epha3 and Epha5, whereas loss of Olig2 resulted in reduction of this Ephas-negative area and the corresponding expansion of the Ephas-positive TE. Dissociated cultures of thalamic progenitor cells demonstrated that substrate-bound EphA3 suppresses neurite extension from dorsal thalamic neurons. These results indicate that Olig2 is involved in correct formation of the prethalamus, which leads to exclusion of the EphA3-expressing region and is crucial for proper TCA formation. Our observation is the first report showing the molecular mechanisms underlying how the prethalamus acts on initial thalamocortical projection formation.

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“…These studies have found EphB2 fusion protein and EphB3 mRNA expression in the CC during the development of this tract Orioli et al, 1996), which occurs between embryonic day 15 (E15) and E18 in the mouse CNS (Rash and Richards, 2001). In addition, EphA receptors were also detected in CC fibers, suggesting a possible function for these molecules in CC development (Kudo et al, 2005). Analysis of EphB2 knock-out (EphB2 KO ) and EphB3 KO mice supported a role for Eph receptors in CC and AC midline pathfinding Orioli et al, 1996).…”

Section: Introductionmentioning

confidence: 88%

Multiple Eph Receptors and B-Class Ephrins Regulate Midline Crossing of Corpus Callosum Fibers in the Developing Mouse Forebrain

Mendes¹,

Henkemeyer²,

Liebl³

2006

J. Neurosci.

105

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Agenesis of the corpus callosum (CC) is a rare birth defect that occurs in isolated conditions and in combination with other developmental cerebral abnormalities. Recent identification of families of growth and guidance molecules has generated interest in the mechanisms that regulate callosal growth. One family, ephrins and Eph receptors, has been implicated in mediating midline pathfinding decisions; however, the complexity of these interactions has yet to be unraveled. Our studies shed light on which B-class ephrins and Eph receptors function to regulate CC midline growth and how these molecules interact with important guideposts during development. We show that multiple Eph receptors (B1, B2, B3, and A4) and B-class ephrins (B1, B2, and B3) are present and function in developing forebrain callosal fibers based on both spatial and temporal expression patterns and analysis of gene-targeted knock-out mice. Defects are most pronounced in the combination double knock-out mice, suggesting that compensatory mechanisms exist for several of these family members. Furthermore, these CC defects range from mild hypoplasia to complete agenesis and Probst's bundle formation. Further analysis revealed that Probst's bundle formation may reflect aberrant glial formations and/or altered sensitivity of CC axons to other guidance cues. Our results support a significant role for ephrins and Eph receptors in CC development and may provide insight to possible mechanisms involved in axon midline crossing and human disorder.

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Expression profiles of EphA3 at both the RNA and protein level in the developing mammalian forebrain

Cited by 39 publications

References 32 publications

EphrinA5 protein distribution in the developing mouse brain

EphrinA5 protein distribution in the developing mouse brain

Development of the prethalamus is crucial for thalamocortical projection formation and is regulated by Olig2

Multiple Eph Receptors and B-Class Ephrins Regulate Midline Crossing of Corpus Callosum Fibers in the Developing Mouse Forebrain

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