Smad-interacting protein-1 (Zfhx1b) acts upstream of Wnt signaling in the mouse hippocampus and controls its formation

Miquelajáuregui, Amaya; Putte, Tom Van de; Polyakov, Alexander S.; Nityanandam, Anjana; Boppana, Sridhar; Seuntjens, Eve; Karabinos, Anton; Higashi, Youichirou; Huylebroeck, Danny; Tarabykin, Victor

doi:10.1073/pnas.0609863104

Cited by 86 publications

(110 citation statements)

References 38 publications

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“…Moreover, BMP2 and BMP4 induce Dkk1 expression during limb development in mouse and chicken (Grotewold and Ruther, 2002;Mukhopadhyay et al, 2001). In addition, other studies suggest possible cross-talk between SFRPs and BMP signaling (Ellies et al, 2000;Miquelajauregui et al, 2007;Oshima et al, 2005). However, the present study provides the first in vivo evidence that BMP/TGF relies on SMAD4 to regulate Dkk1 and Sfrp1 expression during dentinogenesis.…”

Section: Dkk1 and Sfrp1 Are Downstream Targets Of Smad4supporting

confidence: 44%

SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis

Huang

et al. 2011

Development

102

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SUMMARYTGF/BMP signaling regulates the fate of multipotential cranial neural crest (CNC) cells during tooth and jawbone formation as these cells differentiate into odontoblasts and osteoblasts, respectively. The functional significance of SMAD4, the common mediator of TGF/BMP signaling, in regulating the fate of CNC cells remains unclear. In this study, we investigated the mechanism of SMAD4 in regulating the fate of CNC-derived dental mesenchymal cells through tissue-specific inactivation of Smad4. Ablation of Smad4 results in defects in odontoblast differentiation and dentin formation. Moreover, ectopic bone-like structures replaced normal dentin in the teeth of Osr2-IresCre;Smad4 fl/fl mice. Despite the lack of dentin, enamel formation appeared unaffected in Osr2-IresCre;Smad4 fl/fl mice, challenging the paradigm that the initiation of enamel development depends on normal dentin formation. At the molecular level, loss of Smad4 results in downregulation of the WNT pathway inhibitors Dkk1 and Sfrp1 and in the upregulation of canonical WNT signaling, including increased -catenin activity. More importantly, inhibition of the upregulated canonical WNT pathway in Osr2-IresCre;Smad4 fl/fl dental mesenchyme in vitro partially rescued the CNC cell fate change. Taken together, our study demonstrates that SMAD4 plays a crucial role in regulating the interplay between TGF/BMP and WNT signaling to ensure the proper CNC cell fate decision during organogenesis.

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Section: Dkk1 and Sfrp1 Are Downstream Targets Of Smad4supporting

confidence: 44%

SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis

Huang

et al. 2011

Development

102

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“…We have previously shown that deletion of Sip1 in postmitotic neurons has severe effects on cortical development (Miquelajauregui et al, 2007;Seuntjens et al, 2009). We had demonstrated that Sip1 deletion in young neocortical neurons changes the proportion of DL versus UL neurons.…”

Section: Resultsmentioning

confidence: 97%

Ntf3 acts downstream of Sip1 in cortical postmitotic neurons to control progenitor cell fate through feedback signaling

et al. 2014

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Cortical progenitors undergo progressive fate restriction, thereby sequentially producing the different layers of the neocortex. However, how these progenitors precisely change their fate remains highly debatable. We have previously shown the existence of cortical feedback mechanisms wherein postmitotic neurons signal back to the progenitors and promote a switch from neurogenesis to gliogenesis. We showed that Sip1 (Zeb2), a transcriptional repressor, controls this feedback signaling. A similar mechanism was also suggested to control neuronal cell type specification; however, the underlying mechanism was not identified. Here, we provide direct evidence that in the developing mouse neocortex, Ntf3, a Sip1 target neurotrophin, acts as a feedback signal between postmitotic neurons and progenitors, promoting both apical progenitor (AP) to basal progenitor (BP) and deep layer (DL) to upper layer (UL) cell fate switches. We show that specific overexpression of Ntf3 in neocortical neurons promotes an overproduction of BP at the expense of AP. This shift is followed by a decrease in DL and an increase in UL neuronal production. Loss of Ntf3, by contrast, causes an increase in layer VI neurons but does not rescue the Sip1 mutant phenotype, implying that other parallel pathways also control the timing of progenitor cell fate switch.

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“…Sip1 transcripts are detected at the onset of neurogenesis in the postmitotic cells of the mouse neocortex, with barely detectable levels in progenitors 18 . By immunohistochemistry, we found high Sip1 protein levels in the cortical plate, but none in progenitors (Fig.…”

Section: Sip1 Levels Are High In Postmitotic Neocortical Cellsmentioning

confidence: 99%

Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors

et al. 2009

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The fate of cortical progenitors, which progressively generate neurons and glial cells during development, is determined by temporally and spatially regulated signaling mechanisms. We found that the transcription factor Sip1 (Zfhx1b), which is produced at high levels in postmitotic neocortical neurons, regulates progenitor fate non-cell autonomously. Conditional deletion of Sip1 in young neurons induced premature production of upper-layer neurons at the expense of deep layers, precocious and increased generation of glial precursors, and enhanced postnatal astrocytogenesis. The premature upper-layer generation coincided with overexpression of the neurotrophin-3 (Ntf3) gene and upregulation of fibroblast growth factor 9 (Fgf9) gene expression preceded precocious gliogenesis. Exogenous application of Fgf9 to mouse cortical slices induced excessive generation of glial precursors in the germinal zone. Our data suggest that Sip1 restrains the production of signaling factors in postmitotic neurons that feed back to progenitors to regulate the timing of cell fate switch and the number of neurons and glial cells throughout corticogenesis.

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Smad-interacting protein-1 (Zfhx1b) acts upstream of Wnt signaling in the mouse hippocampus and controls its formation

Cited by 86 publications

References 38 publications

SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis

SMAD4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis

Ntf3 acts downstream of Sip1 in cortical postmitotic neurons to control progenitor cell fate through feedback signaling

Sip1 regulates sequential fate decisions by feedback signaling from postmitotic neurons to progenitors

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