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The Drosophila Sp8 transcription factor Buttonhead prevents premature differentiation of intermediate neural progenitors.

Xie Y, Li X, Zhang X, Mei S, Li H, Urso A, Zhu S - Elife (2014)

Bottom Line: We provide evidence to demonstrate that Btd prevents the premature differentiation by suppressing the expression of the homeodomain protein Prospero in immature INPs.We further show that Btd functions cooperatively with the Ets transcription factor Pointed P1 to promote the generation of INPs.Thus, our work reveals a critical mechanism that prevents premature differentiation and cell cycle exit of Drosophila INPs.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, United States.

ABSTRACT
Intermediate neural progenitor cells (INPs) need to avoid differentiation and cell cycle exit while maintaining restricted developmental potential, but mechanisms preventing differentiation and cell cycle exit of INPs are not well understood. In this study, we report that the Drosophila homolog of mammalian Sp8 transcription factor Buttonhead (Btd) prevents premature differentiation and cell cycle exit of INPs in Drosophila larval type II neuroblast (NB) lineages. We show that the loss of Btd leads to elimination of mature INPs due to premature differentiation of INPs into terminally dividing ganglion mother cells. We provide evidence to demonstrate that Btd prevents the premature differentiation by suppressing the expression of the homeodomain protein Prospero in immature INPs. We further show that Btd functions cooperatively with the Ets transcription factor Pointed P1 to promote the generation of INPs. Thus, our work reveals a critical mechanism that prevents premature differentiation and cell cycle exit of Drosophila INPs.

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Related in: MedlinePlus

Expression of mouse Sp8 (mSp8).(A–A′′) and Drosophila Btd (B–B′′) rescues the loss of mature INPs in btd mutant type II NB clones. Multiple mature INPs are observed in btd mutant type II NB clone that expresses UAS-mSp8 (A–A′′) or UAS-btd (B–B′′). Type II NBs, Ase− immature INPs, Ase+ immature INPs, and mature INPs are indicated by asterisks, open arrows, solid arrows, and arrowheads, respectively.DOI:http://dx.doi.org/10.7554/eLife.03596.004
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fig1s1: Expression of mouse Sp8 (mSp8).(A–A′′) and Drosophila Btd (B–B′′) rescues the loss of mature INPs in btd mutant type II NB clones. Multiple mature INPs are observed in btd mutant type II NB clone that expresses UAS-mSp8 (A–A′′) or UAS-btd (B–B′′). Type II NBs, Ase− immature INPs, Ase+ immature INPs, and mature INPs are indicated by asterisks, open arrows, solid arrows, and arrowheads, respectively.DOI:http://dx.doi.org/10.7554/eLife.03596.004

Mentions: To confirm that the loss of INPs indeed results from the knockdown of Btd rather than off-target effects of UAS-Btd RNAi, we generated btd mutant type II NB clones using two loss-of-function alleles, btdXA and btdXG81 (Wimmer et al., 1993; Estella and Mann, 2010). Consistent with the Btd RNAi knockdown, all btdXG81 mutant and 90% of btdXA mutant type II NB clones failed to generate any mature INPs except for 4–6 Ase+ Dpn− cells (Figure 1D–F′,G–H). Moreover, about 40% of btd mutant type II NBs ectopically express Ase, making them appear as type I NB lineages (Figure 1E). The loss of INPs resulting from the Btd RNAi knockdown and btd loss-of-function mutations suggests that Btd is required for the generation of INPs. Remarkably, the loss of INPs in btd mutant clones can be similarly rescued by the expression of mouse Sp8 or Drosophila Btd (Figure 1—figure supplement 1), suggesting that mammalian Sp8 could have a conserved role in promoting the generation of transient amplifying INPs.


The Drosophila Sp8 transcription factor Buttonhead prevents premature differentiation of intermediate neural progenitors.

Xie Y, Li X, Zhang X, Mei S, Li H, Urso A, Zhu S - Elife (2014)

Expression of mouse Sp8 (mSp8).(A–A′′) and Drosophila Btd (B–B′′) rescues the loss of mature INPs in btd mutant type II NB clones. Multiple mature INPs are observed in btd mutant type II NB clone that expresses UAS-mSp8 (A–A′′) or UAS-btd (B–B′′). Type II NBs, Ase− immature INPs, Ase+ immature INPs, and mature INPs are indicated by asterisks, open arrows, solid arrows, and arrowheads, respectively.DOI:http://dx.doi.org/10.7554/eLife.03596.004
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221738&req=5

fig1s1: Expression of mouse Sp8 (mSp8).(A–A′′) and Drosophila Btd (B–B′′) rescues the loss of mature INPs in btd mutant type II NB clones. Multiple mature INPs are observed in btd mutant type II NB clone that expresses UAS-mSp8 (A–A′′) or UAS-btd (B–B′′). Type II NBs, Ase− immature INPs, Ase+ immature INPs, and mature INPs are indicated by asterisks, open arrows, solid arrows, and arrowheads, respectively.DOI:http://dx.doi.org/10.7554/eLife.03596.004
Mentions: To confirm that the loss of INPs indeed results from the knockdown of Btd rather than off-target effects of UAS-Btd RNAi, we generated btd mutant type II NB clones using two loss-of-function alleles, btdXA and btdXG81 (Wimmer et al., 1993; Estella and Mann, 2010). Consistent with the Btd RNAi knockdown, all btdXG81 mutant and 90% of btdXA mutant type II NB clones failed to generate any mature INPs except for 4–6 Ase+ Dpn− cells (Figure 1D–F′,G–H). Moreover, about 40% of btd mutant type II NBs ectopically express Ase, making them appear as type I NB lineages (Figure 1E). The loss of INPs resulting from the Btd RNAi knockdown and btd loss-of-function mutations suggests that Btd is required for the generation of INPs. Remarkably, the loss of INPs in btd mutant clones can be similarly rescued by the expression of mouse Sp8 or Drosophila Btd (Figure 1—figure supplement 1), suggesting that mammalian Sp8 could have a conserved role in promoting the generation of transient amplifying INPs.

Bottom Line: We provide evidence to demonstrate that Btd prevents the premature differentiation by suppressing the expression of the homeodomain protein Prospero in immature INPs.We further show that Btd functions cooperatively with the Ets transcription factor Pointed P1 to promote the generation of INPs.Thus, our work reveals a critical mechanism that prevents premature differentiation and cell cycle exit of Drosophila INPs.

View Article: PubMed Central - PubMed

Affiliation: Department of Neuroscience and Physiology, State University of New York Upstate Medical University, Syracuse, United States.

ABSTRACT
Intermediate neural progenitor cells (INPs) need to avoid differentiation and cell cycle exit while maintaining restricted developmental potential, but mechanisms preventing differentiation and cell cycle exit of INPs are not well understood. In this study, we report that the Drosophila homolog of mammalian Sp8 transcription factor Buttonhead (Btd) prevents premature differentiation and cell cycle exit of INPs in Drosophila larval type II neuroblast (NB) lineages. We show that the loss of Btd leads to elimination of mature INPs due to premature differentiation of INPs into terminally dividing ganglion mother cells. We provide evidence to demonstrate that Btd prevents the premature differentiation by suppressing the expression of the homeodomain protein Prospero in immature INPs. We further show that Btd functions cooperatively with the Ets transcription factor Pointed P1 to promote the generation of INPs. Thus, our work reveals a critical mechanism that prevents premature differentiation and cell cycle exit of Drosophila INPs.

Show MeSH
Related in: MedlinePlus