Molecular characterization, structure and developmental expression of Megane bHLH factor

Guimerà, Jordi; Weisenhorn, Daniela M. Vogt; Echevarrı́a, Diego; Wurst, Wolfgang

doi:10.1016/j.gene.2006.02.026

Cited by 15 publications

(20 citation statements)

References 22 publications

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“…This lack of GABAergic neurons takes places in the most rostral and most caudal part of the IC (see Fig. S1B,E in the supplementary material), where Mgn is normally expressed (Guimera et al, 2006). Strikingly, in the ventral part of the postnatal mesencephalon and in other brain areas outside the colliculi, no obvious changes of the GABAergic neurons could be detected as determined by the presence of Gad65 and Gad67…”

Section: Mgn Is Essential For the Development Of Gabaergic Neurons Ofmentioning

confidence: 94%

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Megane/Heslike is required for normal GABAergic differentiation in the mouse superior colliculus

2006

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The mouse Mgn protein (Helt) is structurally related to the neurogenic Drosophila hairy and Enhancer of split [h/E(spl)] proteins, but its unique structural properties distinguish it from other members of the family. Mgn expression shows a spatiotemporal correlation with GABAergic markers in several brain regions. We report here that homozygous Mgn-null mice die between the second and the fifth postnatal week of age, and show a complete depletion of Gad65 and Gad67 expression in the superior colliculus and a reduction in the inferior colliculus. Other brain regions, as well as other neural systems, are not affected. The progenitor GABAergic cells appear to be generated in right numbers but fail to become GABAergic neurons. The phenotype of the mice is consistent with reduced GABAergic activity. Thus, our in vivo study provides evidence that Mgn is the key regulator of GABAergic neurons, controlling their specification in the dorsal midbrain. Another conclusion from our results is that the function of Mgn shows a previously unrecognized role for h/E(spl)-related transcription factors in the dorsal midbrain GABAergic cell differentiation. Vertebrate h/E(spl)-related genes can no longer be regarded solely as a factors that confer generic neurogenic properties, but as key components for the subtype-neuronal identity in the mammalian CNS.

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Section: Mgn Is Essential For the Development Of Gabaergic Neurons Ofmentioning

confidence: 94%

“…We isolated a new member of the h/E(spl)-related bHLH protein referred to as megane (Mgn; Helt -Mouse Genome Informatics) (Guimera et al, 2006;Miyoshi et al, 2004;Nakatani et al, 2004). Mgn shows an expression pattern restricted to the midbrain at mouse developmental day 9.5 (E9.5).…”

Section: Introductionmentioning

confidence: 99%

Megane/Heslike is required for normal GABAergic differentiation in the mouse superior colliculus

2006

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“…In zebrafish, the basic helixloop-helix (bHLH) transcription factor Her6 represses ngn2 (neurog3 -Zebrafish Information Network) expression affecting the balance between the proneural genes ascl1 and ngn2 and allowing GABAergic neurogenesis (Scholpp et al, 2009). In mouse, as Her6 is expressed in rostral P2 but not in P1, loss of the Ngn2 repressor Ascl1 might lead to Ngn2 upregulation in P1 but might not be sufficient to induce it in pTh-R. Another bHLHOrange (bHLH-O) transcription factor Helt, an Ngn repressor in the embryonic midbrain (Nakatani et al, 2007), is also expressed in the diencephalon and is required for normal GABAergic neuron development in the posterior pretectum (Guimera et al, 2006a;Guimera et al, 2006b). Interestingly, loss of Ascl1 inhibited cellcycle exit in P3, but appeared to promote it in pTh-R. A recent study identified both cell-cycle repressors and promoters as Ascl1 targets .…”

Section: Ascl1 Differently Regulates Gabaergic Neuron Differentiationmentioning

confidence: 99%

Transcriptional regulatory mechanisms underlying the GABAergic neuron fate in different diencephalic prosomeres

et al. 2012

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SUMMARYDiverse mechanisms regulate development of GABAergic neurons in different regions of the central nervous system. We have addressed the roles of a proneural gene, Ascl1, and a postmitotic selector gene, Gata2, in the differentiation of GABAergic neuron subpopulations in three diencephalic prosomeres: prethalamus (P3), thalamus (P2) and pretectum (P1). Although the different proliferative progenitor populations of GABAergic neurons commonly express Ascl1, they have distinct requirements for it in promotion of cell-cycle exit and GABAergic neuron identity. Subsequently, Gata2 is activated as postmitotic GABAergic precursors are born. In P1, Gata2 regulates the neurotransmitter identity by promoting GABAergic and inhibiting glutamatergic neuron differentiation. Interestingly, Gata2 defines instead the subtype of GABAergic neurons in the rostral thalamus (pTh-R), which is a subpopulation of P2. Without Gata2, the GABAergic precursors born in the pTh-R fail to activate subtype-specific markers, but start to express genes typical of GABAergic precursors in the neighbouring P3 domain. Thus, our results demonstrate diverse mechanisms regulating differentiation of GABAergic neuron subpopulations and suggest a role for Gata2 as a selector gene of both GABAergic neuron neurotransmitter and prosomere subtype identities in the developing diencephalon. Our results demonstrate for the first time that neuronal identities between distinct prosomeres can still be transformed in postmitotic neuronal precursors.

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“…1A,B), we next determined if -catenin is required in the pTH-C domain to suppress not only prethalamic fate, but also pTH-R fate. For this purpose, we first identified transcription factors that are expressed in pTH-R but not in the prethalamus or pTH-C. We found that Helt (Nakatani et al, 2007;Miyoshi et al, 2004;Guimera et al, 2006) and Gata2 (Kala et al, 2009) were specifically expressed in pTH-R progenitor cells and Gata2 and Gata3 can be used as markers of postmitotic, pTH-R-derived cells (supplementary material Fig. S4).…”

Section: Deletion Of Ctnnb1 Causes a Pth-c To Pth-r Fate Switchmentioning

confidence: 99%

β-Catenin signaling specifies progenitor cell identity in parallel with Shh signaling in the developing mammalian thalamus

et al. 2012

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SUMMARYNeural progenitor cells within the developing thalamus are spatially organized into distinct populations. Their correct specification is critical for generating appropriate neuronal subtypes in specific locations during development. Secreted signaling molecules, such as sonic hedgehog (Shh) and Wnts, are required for the initial formation of the thalamic primordium. Once thalamic identity is established and neurogenesis is initiated, Shh regulates the positional identity of thalamic progenitor cells. Although Wnt/-catenin signaling also has differential activity within the thalamus during this stage of development, its significance has not been directly addressed. In this study, we used conditional gene manipulations in mice and explored the roles of -catenin signaling in the regional identity of thalamic progenitor cells. We found -catenin is required during thalamic neurogenesis to maintain thalamic fate while suppressing prethalamic fate, demonstrating that regulation of regional fate continues to require extrinsic signals. These roles of -catenin appeared to be mediated at least partly by regulating two basic helix-loop-helix (bHLH) transcription factors, Neurog1 and Neurog2. -Catenin and Shh signaling function in parallel to specify two progenitor domains within the thalamus, where individual transcription factors expressed in each progenitor domain were regulated differently by the two signaling pathways. We conclude that -catenin has multiple functions during thalamic neurogenesis and that both Shh and -catenin pathways are important for specifying distinct types of thalamic progenitor cells, ensuring that the appropriate neuronal subtypes are generated in the correct locations.

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Molecular characterization, structure and developmental expression of Megane bHLH factor

Cited by 15 publications

References 22 publications

Megane/Heslike is required for normal GABAergic differentiation in the mouse superior colliculus

Megane/Heslike is required for normal GABAergic differentiation in the mouse superior colliculus

Transcriptional regulatory mechanisms underlying the GABAergic neuron fate in different diencephalic prosomeres

β-Catenin signaling specifies progenitor cell identity in parallel with Shh signaling in the developing mammalian thalamus

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