The GATA2 transcription factor negatively regulates the proliferation of neuronal progenitors

Wakil, Abeer El; Francius, Cédric; Wolff, Annie; Pleau-Varet, Jocelyne; Nardelli, Jeannette

doi:10.1242/dev.02377

Cited by 48 publications

(58 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Accordingly, GATA-2 overexpression has been shown to cause differentiation of human neuroblastoma SK-N-BE2 cells (Kaneko et al, 2006). In addition, Gata-2 overexpression arrested the proliferation of mouse neuroblastoma cells (NB2a), yet without induction of differentiation (El Wakil et al, 2006). In this context, GATA-2 may act on regulators of cell cycle components and/or shut-off the Notch pathway (El Wakil et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Gata-2 overexpression arrested the proliferation of mouse neuroblastoma cells (NB2a), yet without induction of differentiation (El Wakil et al, 2006). In this context, GATA-2 may act on regulators of cell cycle components and/or shut-off the Notch pathway (El Wakil et al, 2006). Although FOG-2 is likely to interact with any GATA protein, our data obtained in neuroblastoma specimens suggest a predominant interaction with GATA-2 and/or GATA-3; in addition, the interaction between FOG-2 and GATA-4 could be disturbed.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

GATA factors in human neuroblastoma: distinctive expression patterns in clinical subtypes

et al. 2009

View full text Add to dashboard Cite

BACKGROUND: The aim of this study is to elucidate the expression patterns of GATA transcription factors in neuroblastoma and the developing sympathetic nervous system (SNS). METHODS: GATA-2, -3 and -4 and their cofactor friend-of-GATA (FOG)-2 were investigated in primary neuroblastoma by immunohistochemistry, real-time RT-PCR (n ¼ 73) and microarray analysis (n ¼ 251). In addition, GATA-2, -3 and FOG-2 expression was determined by northern-blot hybridisation. In the developing murine SNS, Gata-4 and Fog-2 were examined by immunohistochemistry. RESULTS: Although Gata-2, -3 and Fog-2 are expressed in the developing nervous system, Gata-4 was not detected. In contrast, protein expression of all factors was observed in human neuroblastoma. Northern-blot hybridisation and real-time RT-PCR suggested specific expression patterns of the four genes in primary neuroblastoma, but did not show unequivocal results. In the large cohort examined by microarrays, a significant association of GATA-2, -3 and FOG-2 expression with low-risk features was observed, whereas GATA-4 mRNA levels correlated with MYCN-amplification. CONCLUSION: The transcription factors GATA-2 and -3, which are essential for normal SNS development, and their cofactor FOG-2 are downregulated in aggressive but not in favourable neuroblastoma. In contrast, upregulation of GATA-4 appears to be a common feature of this malignancy and might contribute to neuroblastoma pathogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

GATA factors in human neuroblastoma: distinctive expression patterns in clinical subtypes

et al. 2009

View full text Add to dashboard Cite

show abstract

“…21 However, forced overexpression of GATA2 in bone marrow hematopoietic stem/progenitor cells does not enhance proliferation, but instead induces differentiation into monocytic/ granulocytic lineages, or into eosinophils. [22][23][24] Overexpression of GATA2 also inhibits the proliferation of neuroepithelial and neuroblastoma cells, 25 and exogenous expression of GATA2/ estrogen-receptor chimeric protein stops the proliferation of Ba/F3 cells in G 1 phase, accompanied by the accumulation of p21 Cip1/Waf1 and p27 Kip1 . 26 On the other hand, wild-type GATA2 (but not GATA2/estrogen-receptor chimeric protein) induces cell proliferation, when expressed in hematopoietic progenitor cells derived from embryonic stem cells.…”

Section: Introductionmentioning

confidence: 99%

Cell-cycle–dependent oscillation of GATA2 expression in hematopoietic cells

Koga

Yamada

Abe

et al. 2007

Blood

View full text Add to dashboard Cite

In vitro manipulation of hematopoietic stem cells (HSCs) is a key issue in both transplantation therapy and regenerative medicine, and thus new methods are required to achieve HSC expansion with self-renewal. GATA2 is a transcription factor controlling pool size of HSCs. Of interest, continuous overexpression of GATA2 does not induce HSC proliferation. In this report, we demonstrate that GATA2 expression, in leukemic and normal hematopoietic cells, oscillates during the cell cycle, such that expression is high in S phase but low in G 1 /S and M phase.GATA2 binding to target Bcl-X gene also oscillates in accordance with GATA2 expression. Using a green fluorescent protein (GFP)-GATA2 fusion protein, we demonstrate cell-cycle-specific activity of proteasome-dependent degradation of GATA2. Immunoprecipitation/immunoblotting analysis demonstrated phosphorylation of GATA2 at cyclin-dependent kinase (Cdk)-consensus motifs, S/T 0 P ؉1 , and interaction of GATA2 with Cdk2/ cyclin A2-, Cdk2/cyclin A2-, and Cdk4/ cyclin D1-phosphorylated GATA2 in vitro. Mutants in phosphorylation motifs exhibited altered expression profiles of GFP-GATA2 domain fusion proteins. These results indicate that GATA2 phosphorylation by Cdk/cyclin systems is responsible for the cell-cycle-dependent regulation of GATA2 expression, and suggest the possibility that a cell-cycle-specific "onoff" response of GATA2 expression may control hematopoietic-cell proliferation and survival. IntroductionHematopoietic stem cells (HSCs) give rise to the immunohematopoietic system throughout the lifetime of host animals. 1 HSCs have distinctive systems regulating their proliferation and differentiation. These systems maintain steady-state hematopoiesis, and respond to stresses, including infection, hypoxia, and blood loss. 1,2 Two types of cell division occur in HSCs: one type produces differentiated daughter cells to supply mature blood cells, while the other type reproduces HSCs (self-renewal division) to maintain life-long hematopoiesis. 1,2 Of interest, in the bone marrow reservoir of HSCs, more than 70% of bone marrow HSCs are quiescent (G 0 phase), maintaining high proliferative capacity and pluripotency. 3 In contrast, their quiescent mature progeny generally lack the capacity for growth and division.Directing the expansion of HSCs in vitro is an urgent problem that must be solved to meet the needs of transplantation therapy and to fulfill the promise of regenerative medicine. 4 HSC self-renewal and maturation divisions appear to be controlled, at least in part, by transcription factors (MEL/ELF4, 5 Gfi1 6,7 ), and also by cellcycle regulatory factors (cyclin-dependent kinase (Cdk) inhibitor, p21 Cip1/Waf1 , 8 p18 INK4C 9 phosphatase and tensin homologue (PTEN), 10 c-Myc, 11 and Myc antagonist, Mad 1 12 ). Analysis of mice deficient in Gfi1, 6,7 p21 Cip1/Waf1 , 8 or PTEN 10 revealed increased marrow HSC cycling and subsequent exhaustion of HSCs, and suggest possible cooperation between transcription factors and cell-cycle regulators.GATA2 is a member of th...

show abstract

“…In addition, loss of Gata2 in midbrain leads to a complete fate switch of GABAergic neural progenitors to glutamatergic fate, whereas it did not affect the proliferation of progenitors in this region (Kala et al, 2009). On the other hand, in caudal hindbrain and spinal cord, Gata2 expression inhibits proliferation and forces cycling neural progenitors to a quiescent and differentiating state by interfering with cell cycle regulators and Notch pathway (El Wakil et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Gata2 is required for the development of inner ear semicircular ducts and the surrounding perilymphatic space

Haugas¹,

Lilleväli²,

Hakanen³

et al. 2010

Developmental Dynamics

View full text Add to dashboard Cite

*Gata2 has essential roles in the development of many organs. During mouse inner ear morphogenesis, it is expressed in otic vesicle and the surrounding periotic mesenchyme from early on, but no defects in the ear development of Gata2 null mice have been observed before lethality at embryonic day (E) 10.5. Here, we used conditional gene targeting to reveal the role of Gata2 at later stages of inner ear development. We show that Gata2 is critically required from E14.5-E15.5 onward for vestibular morphogenesis. Without Gata2 the semicircular ducts fail to grow to their normal size and the surrounding mesenchymal cells are not removed properly to generate the perilymphatic space. Gata2 is the first factor known to control the clearing of the vestibular perilymphatic mesenchyme, but interestingly, it is not required for the formation of the cochlear perilymphatic areas, suggesting distinct molecular control for these processes.

show abstract

The GATA2 transcription factor negatively regulates the proliferation of neuronal progenitors

Cited by 48 publications

References 52 publications

GATA factors in human neuroblastoma: distinctive expression patterns in clinical subtypes

GATA factors in human neuroblastoma: distinctive expression patterns in clinical subtypes

Cell-cycle–dependent oscillation of GATA2 expression in hematopoietic cells

Gata2 is required for the development of inner ear semicircular ducts and the surrounding perilymphatic space

Contact Info

Product

Resources

About