Ascl1 is a required downstream effector of Gsx gene function in the embryonic mouse telencephalon

Wang, Bei; Waclaw, Ronald R.; Allen, Zegary J; Guillemot, François; Campbell, Kenneth

doi:10.1186/1749-8104-4-5

Cited by 72 publications

(96 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…E18.5) when Sp8-expressing neuroblasts were beginning to reseed the dLGE. This is presumably the result of the Gsx1-and Ascl1/Dlx-led restoration of LGE identity (Toresson and Campbell, 2001;Yun et al, 2003;Wang et al, 2009), which appears to restore neurogenesis and halt ectopic OPC specification. Despite this apparent normalization of VZ progenitors, these transiently generated Gsx2-derived OPCs migrate from the SVZ into the adjacent cerebral cortex and expand.…”

Section: Discussionmentioning

confidence: 99%

“…2F), suggesting that they are early OPCs arising from mutant dLGE progenitors. At later stages of embryogenesis the reduced neurogenesis and altered molecular specification in the Gsx2 mutant LGE begins to recover, largely because of the dorsal expansion of Gsx1, and return of Ascl1 and Dlx expression to LGE progenitors (Toresson and Campbell, 2001;Yun et al, 2003;Wang et al, 2009). Thus, we next examined mutant LGE progenitors at E18.5 and found that the ectopic clump of Olig2-positive cells in the dLGE SVZ was no longer obvious ( Fig.…”

Section: Transient Increase In Opc Specification In the Gsx2 Mutant Lgementioning

confidence: 99%

See 1 more Smart Citation

The homeobox gene Gsx2 controls the timing of oligodendroglial fate specification in mouse lateral ganglionic eminence progenitors

et al. 2013

Self Cite

View full text Add to dashboard Cite

SUMMARYThe homeobox gene Gsx2 has previously been shown to be required for the specification of distinct neuronal subtypes derived from lateral ganglionic eminence (LGE) progenitors at specific embryonic time points. However, its role in the subsequent generation of oligodendrocytes from these progenitors remains unclear. We have utilized conditional gain-of-function and loss-of-function approaches in order to elucidate the role of Gsx2 in the switch between neurogenesis and oligodendrogenesis within the embryonic ventral telencephalon. In the absence of Gsx2 expression, an increase in oligodendrocyte precursor cells (OPCs) with a concomitant decrease in neurogenesis is observed in the subventricular zone of the LGE at mid-stages of embryogenesis (i.e. E12.5-15.5), which subsequently leads to an increased number of Gsx2-derived OPCs within the adjacent mantle regions of the cortex before birth at E18.5. Moreover, using Olig2 cre to conditionally inactivate Gsx2 throughout the ventral telencephalon with the exception of the dorsal (d)LGE, we found that the increase in cortical OPCs in Gsx2 germline mutants are derived from dLGE progenitors. We also show that Ascl1 is required for the expansion of these dLGE-derived OPCs in the cortex of Gsx2 mutants. Complementing these results, gain-of-function experiments in which Gsx2 was expressed throughout most of the late-stage embryonic telencephalon (i.e. E15.5-18.5) result in a significant decrease in the number of cortical OPCs. These results support the notion that high levels of Gsx2 suppress OPC specification in dLGE progenitors and that its downregulation is required for the transition from neurogenesis to oligodendrogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Transient Increase In Opc Specification In the Gsx2 Mutant Lgementioning

confidence: 99%

The homeobox gene Gsx2 controls the timing of oligodendroglial fate specification in mouse lateral ganglionic eminence progenitors

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…It must be, therefore, that other factors can substitute for the absence of Gsx1 in driving the differentiation of LGE progenitors. In this respect, Ascl1 (Mash1), which is known to play an important role in LGE progenitor maturation (38,39), is required for the partial compensatory role of Gsx1 in the Gsx2 mutant telencephalon (16).…”

Section: Discussionmentioning

confidence: 99%

“…However, the specific cellular expression of Gsx1 protein has not been described due to the lack of a well-characterized antibody. Our previous study found that Gsx1, as detected by Gsx1/2 antibody (12), is expressed by a subset of progenitors in the Gsx2 mutant LGE, which are concentrated basally at the VZ/SVZ boundary (16). Using Gsx1-EGFP BAC transgenic mice (together with the Gsx1/2 antibody), we show here that, even in wild-type embryos, Gsx1-expressing progenitors of the vLGE and MGE appear to be clustered at the VZ/SVZ boundary.…”

Section: Discussionmentioning

confidence: 99%

“…From embryonic day (E) 12.5 and onward, Gsx2 is expressed at a high level in progenitors of the dorsal LGE (dLGE) and relatively lower level in the ventral LGE (vLGE) and MGE progenitors, whereas Gsx1 is expressed mainly in the MGE and vLGE (4,10,(14)(15)(16)(17)(18). The graded Gsx2 expression pattern in LGE progenitors has recently been implicated in the distinct neuronal output of the dLGE versus the vLGE (17).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Homeobox genes Gsx1 and Gsx2 differentially regulate telencephalic progenitor maturation

Pei¹,

Wang²,

Chen

et al. 2011

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

Self Cite

105

View full text Add to dashboard Cite

Homeobox genes Gsx1 and Gsx2 (formerly Gsh1 and Gsh2) are among the earliest transcription factors expressed in neuronal progenitors of the lateral ganglionic eminence (LGE) in the ventral telencephalon. Gsx2 is required for the early specification of LGE progenitor cells and recently has been shown to specify different LGE neuronal subtypes at distinct time points. In Gsx2 mutants, Gsx1 compensates, at least in part, for the loss of Gsx2 in the specification of LGE neuronal subtypes. Because no specific phenotype has been described in Gsx1 mutants, it is unclear what role this factor plays in the development of the ventral telencephalon. Here, we used a gain-of-function approach to express either Gsx1 or Gsx2 throughout the telencephalon and found that Gsx1 functions similarly to Gsx2 in the specification of LGE identity. However, our results show that Gsx1 and Gsx2 differentially regulate the maturation of LGE progenitors. Specifically, Gsx2 maintains LGE progenitors in an undifferentiated state, whereas Gsx1 promotes progenitor maturation and the acquisition of neuronal phenotypes, at least in part, through the down-regulation of Gsx2. These unique results indicate that the two closely related Gsx genes similarly regulate LGE patterning but oppositely control the balance between proliferation and differentiation in the neuronal progenitor pool.cell cycle kinetics | self-renewal

show abstract

Transcriptional Regulation of Olfactory Bulb Neurogenesis

Díaz-Guerra

Pignatelli

Nieto‐Estévez

et al. 2013

The Anatomical Record

View full text Add to dashboard Cite

The neurons in the olfactory bulb originate from molecularly defined and spatially distinct proliferative regions. Glutamatergic projection neurons are generated during the embryonic period in the local ventricular zone of the olfactory bulb, a territory in the dorsal telencephalon in which the transcription factor Pax6 is expressed. Some cells in this zone also express Tbr1, a marker of glutamatergic neurons. By contrast, embryonic olfactory bulb interneurons are derived from Gsx2 expressing cells in the dorsal lateral ganglionic eminence of the ventral telencephalon, and from progenitors outside the dorsal lateral ganglionic eminence, including the olfactory bulb neuroepithelium. Postnatally, interneurons arise from the subventricular zone of the lateral ventricle, although the rostral migratory stream and the olfactory bulb also appear to serve as a source of neurons. Transcription factors are crucial to generate all classes of neurons and glia in the olfactory bulb, both during development and adulthood. In this article, we discuss and propose models on how the spatial and temporal regulation of transcription factor expression controls the self-renewal, proliferation and cell fate of neural stem cells and progenitors, which finally leads to the generation of distinct functional subtypes of neurons in the developing and adult olfactory bulb. Anat Rec, 296:1364Rec, 296: -1382Rec, 296: , 2013. V C 2013 Wiley Periodicals, Inc.Key words: olfactory bulb; neurogenesis; transcription factor; neural stem cells; proliferation; differentiation

show abstract

Ascl1 is a required downstream effector of Gsx gene function in the embryonic mouse telencephalon

Cited by 72 publications

References 40 publications

The homeobox gene Gsx2 controls the timing of oligodendroglial fate specification in mouse lateral ganglionic eminence progenitors

The homeobox gene Gsx2 controls the timing of oligodendroglial fate specification in mouse lateral ganglionic eminence progenitors

Homeobox genes Gsx1 and Gsx2 differentially regulate telencephalic progenitor maturation

Transcriptional Regulation of Olfactory Bulb Neurogenesis

Contact Info

Product

Resources

About