Multiple conserved regulatory domains promote Fezf2 expression in the developing cerebral cortex

Eckler, Matthew J.; Larkin, Kathryn A.; McKenna, William L.; Katzman, Sol; Guo, Chao; Roque, Robin; Visel, Axel; Rubenstein, J L; Chen, Bin

doi:10.1186/1749-8104-9-6

Cited by 25 publications

(28 citation statements)

References 47 publications

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“…In addition, Fezf2 was ectopically expressed in Neurog2-Tg cortices, including in the CP and GZ. Fezf2 is normally expressed in both zones at E12.5 but becomes restricted to the CP by E15.5 (36). Prolonging GZ expression of Fezf2 up to E15.5 in Neurog2-Tgs may expand the temporal window for subcerebral neurogenesis, consistent with our finding that Ctip2 + cells were ectopically generated at E15.5, outside their normal time frame.…”

Section: ;Ascl1supporting

confidence: 89%

“…Conversely, Fezf2, a Satb2 repressor, was ectopically expressed in the CP as well as the GZ in E15.5 Neurog2-Tg cortices (Fig. S6 A and B), the latter reminiscent of the early (E12.5) expression of Fezf2 in wild-type cortical progenitors (36). Thus there is a striking bias toward the production of layer V and VI neuronal phenotypes in Neurog2-Tgs, along with an apparent repression of Satb2 + upper-layer identities.…”

Section: ;Ascl1mentioning

confidence: 99%

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Neurog2 and Ascl1 together regulate a postmitotic derepression circuit to govern laminar fate specification in the murine neocortex

Dennis

Wilkinson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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A derepression mode of cell-fate specification involving the transcriptional repressors Tbr1, Fezf2, Satb2, and Ctip2 operates in neocortical projection neurons to specify six layer identities in sequence. Less well understood is how laminar fate transitions are regulated in cortical progenitors. The proneural genes Neurog2 and Ascl1 cooperate in progenitors to control the temporal switch from neurogenesis to gliogenesis. Here we asked whether these proneural genes also regulate laminar fate transitions. Several defects were observed in the derepression circuit in Neurog2−/− mutants: an inability to repress expression of Tbr1 (a deep layer VI marker) during upper-layer neurogenesis, a loss of Fezf2+ layer V neurons, and precocious differentiation of normally late-born, Satb2 + layer II-IV neurons. Conversely, in stable gain-of-function transgenics, Neurog2 promoted differentiative divisions and extended the period of Tbr1 deep-layer neurogenesis while reducing Satb2+ upper-layer neurogenesis. Similarly, acute misexpression of Neurog2 in early cortical progenitors promoted Tbr1 expression, whereas both Neurog2 and Ascl1 induced Ctip2. However, Neurog2 was unable to influence the derepression circuit when misexpressed in late cortical progenitors, and Ascl1 repressed only Satb2. Nevertheless, neurons derived from late misexpression of Neurog2 and, to a lesser extent, Ascl1, extended aberrant subcortical axon projections characteristic of early-born neurons. Finally, Neurog2 and Ascl1 altered the expression of Ikaros and Foxg1, known temporal regulators. Proneural genes thus act in a context-dependent fashion as early determinants, promoting deeplayer neurogenesis in early cortical progenitors via input into the derepression circuit while also influencing other temporal regulators.neocortex | laminar fate specification | derepression circuit | proneural genes | temporal identity N eocortical neurons project to nearby or distant targets, depending on their molecular identity and correlating with laminar position. Deep-layer corticofugal neurons project subcortically and include layer VI corticothalamic neurons, which target the thalamus, and layer V subcerebral neurons, which project to the spinal cord, basal ganglia, and other distant targets (1). Conversely, layer IV granular neurons are the major site of thalamic input, whereas layer II/III callosal neurons form corticocortical connections. A cross-repressive gene-regulatory network operates in postmitotic projection neurons to specify laminar fates and to repress competing laminar identities (Fig. 1A) (2). Tbr1, a T-box transcription factor expressed in layer VI, specifies a corticothalamic neuronal fate (3) and also represses the expression of Fezf2, a zinc finger transcription factor that specifies a layer V subcerebral identity (4, 5). Fezf2 represses Tbr1 expression and a corticothalamic fate in layer V neurons (6, 7) and also represses the expression of Satb2 (8), an AT-rich DNA-binding protein that specifies a layer II-IV callosal identity (9, 10). In laye...

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Section: ;Ascl1supporting

confidence: 89%

Section: ;Ascl1mentioning

confidence: 99%

Neurog2 and Ascl1 together regulate a postmitotic derepression circuit to govern laminar fate specification in the murine neocortex

Dennis

Wilkinson

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…We have generated stable transgenic mouse lines that expressed a lacZ gene under the control of enhancer 434 and an hsp68 minimal promoter (enhancer 434-lacZ mice) (15). To test whether SATB2 regulates the activity of enhancer 434 in vivo, we generated Emx1-Cre; Satb2…”

Section: Satb2 Promotes the Expression Of Fezf2 A Subcerebral Cell-fatementioning

confidence: 99%

“…, enhancer 434-lacZ, Emx1-Cre, Golli-GFP, and RCE-GFPCre reporter mice were described previously (6,15,16,(36)(37)(38). The …”

Section: Plap/+mentioning

confidence: 99%

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Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex

McKenna

Ortiz-Londono

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Generation of distinct cortical projection neuron subtypes during development relies in part on repression of alternative neuron identities. It was reported that the special AT-rich sequencebinding protein 2 (Satb2) is required for proper development of callosal neuron identity and represses expression of genes that are essential for subcerebral axon development. Surprisingly, Satb2 has recently been shown to be necessary for subcerebral axon development. Here, we unravel a previously unidentified mechanism underlying this paradox. We show that SATB2 directly activates transcription of forebrain embryonic zinc finger 2 (Fezf2) and SRY-box 5 (Sox5), genes essential for subcerebral neuron development. We find that the mutual regulation between Satb2 and Fezf2 enables Satb2 to promote subcerebral neuron identity in layer 5 neurons, and to repress subcerebral characters in callosal neurons. Thus, Satb2 promotes the development of callosal and subcerebral neurons in a cell context-dependent manner.Satb2 | Fezf2 | subcerebral neurons | cerebral cortex | cell fate P rojection neurons in the six-layered neocortex can be classified based on axonal projections. The corticocortical neurons send axons to other areas in the ipsilateral cortex or through the corpus callosum and into the contralateral cortex (i.e., callosal projection neurons). The callosal neurons are distributed throughout layers 2-6, but are most abundant in layers 2 and 3. The corticofugal neurons consist of corticothalamic and subcerebral neurons. The corticothalamic neurons are most abundant in layer 6, and send axons into the thalamus. The subcerebral neurons are located in layer 5, and project axons into the spinal cord, superior colliculus, pons, and other brain areas (1-4).

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Fez family transcription factors: Controlling neurogenesis and cell fate in the developing mammalian nervous system

Eckler

Chen

2014

BioEssays

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Fezf1 and Fezf2 are highly conserved transcription factors that were first identified by their specific expression in the anterior neuroepithelium of Xenopus and zebrafish embryos. These proteins share an N-terminal domain with homology to the canonical engrailed repressor motif and a C-terminal DNA binding domain containing six C2H2 zinc-finger repeats. Over a decade of study indicates that the Fez proteins play critical roles during nervous system development in species as diverse as fruit flies and mice. Herein we discuss recent progress in understanding the functions of Fezf1 and Fezf2 in neurogenesis and cell fate specification during mammalian nervous system development. Going forward we believe that efforts should focus on understanding how expression of these factors is precisely regulated, and on identifying target DNA sequences and interacting partners. Such knowledge may reveal the mechanisms by which Fezf1 and Fezf2 accomplish both independent and redundant functions across diverse tissue and cell types.

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Multiple conserved regulatory domains promote Fezf2 expression in the developing cerebral cortex

Cited by 25 publications

References 47 publications

Neurog2 and Ascl1 together regulate a postmitotic derepression circuit to govern laminar fate specification in the murine neocortex

Neurog2 and Ascl1 together regulate a postmitotic derepression circuit to govern laminar fate specification in the murine neocortex

Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex

Fez family transcription factors: Controlling neurogenesis and cell fate in the developing mammalian nervous system

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