Wnt1-cre-mediated Conditional Loss of Dicer Results in Malformation of the Midbrain and Cerebellum and Failure of Neural Crest and Dopaminergic Differentiation in Mice

Huang, Tianwen; Liu, Yueguang; Huang, Menggui; Zhao, Xiaolin; Cheng, Leping

doi:10.1093/jmcb/mjq008

Cited by 159 publications

(147 citation statements)

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“…Using a mouse with loss of neural crest-derived tissue, we have shown that the neural crest cartilage is needed for the formation of the mesodermally derived stapedial footplate, and in the absence of neural crest cartilage the oval window does not form correctly. In the Wnt1cre-Dicer mice, neural crest cells are able to migrate and are found within the same locations as in control littermates at E11 (Zehir et al, 2010), but cells do not differentiate into cartilage but undergo apoptosis (Huang et al, 2010;Zehir et al, 2010). It is possible, therefore, that the migrating neural crest cells at E11 are able to signal to the otic capsule, positioning the oval window before stapes differentiation.…”

Section: Neural Crest Part Of the Stapes Is Needed For Formation Of Tmentioning

confidence: 99%

“…For this, we took advantage of the Wnt1cre/Dicer mouse, which has been shown to lack cartilages of neural crest origin, including the stapes (Huang et al, 2010). In these mutants, migration of crest into the head appears normal, but the cells do not differentiate into cartilage and high apoptosis is observed in the mandible mesenchyme at E12.5 (Huang et al, 2010;Zehir et al, 2010). At E18.5, in the wild-type mouse the middle ear ossicles can be seen strongly stained with Alcian blue (Fig.…”

Section: Developmental Dynamicsmentioning

confidence: 99%

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The origin of the stapes and relationship to the otic capsule and oval window

Thompson

Ohazama

Sharpe

et al. 2012

Developmental Dynamics

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Background: The stapes, an ossicle found within the middle ear, is involved in transmitting sound waves to the inner ear by means of the oval window. There are several developmental problems associated with this ossicle and the oval window, which cause hearing loss. The developmental origin of these tissues has not been fully elucidated. Results: Using transgenic reporter mice, we have shown that the stapes is of dual origin with the stapedial footplate being composed of cells of both neural crest and mesodermal origin. Wnt1cre/Dicer mice fail to develop neural crest-derived cartilages, therefore, have no middle ear ossicles. We have shown in these mice the mesodermal stapedial footplate fails to form and the oval window is induced but underdeveloped. Conclusions: If the neural crest part of the stapes fails to form the mesodermal part does not develop, indicating that the two parts are interdependent. The stapes develops tightly associated with the otic capsule, however, it is not essential for the positioning of the oval window, suggesting that other tissues, perhaps within the inner ear are needed for oval window placement. Developmental Dynamics 241:1396-1404, 2012. V C 2012 Wiley Periodicals, Inc.Key words: stapes; oval window; neural crest; lineage labeling; mesoderm Key Findings:The stapedial footplate is of neural crest and mesoderm origin. The otic capsule contributes to the stapedial footplate. The neural crest component of the stapedial footplate is needed for development of the mesodermal component and for proper formation of the oval window. The position of the oval window appears independent of the stapes.

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Section: Neural Crest Part Of the Stapes Is Needed For Formation Of Tmentioning

confidence: 99%

Section: Developmental Dynamicsmentioning

confidence: 99%

The origin of the stapes and relationship to the otic capsule and oval window

Thompson

Ohazama

Sharpe

et al. 2012

Developmental Dynamics

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“…Recent studies have revealed the importance of miRNA expression in neural development and differentiation. For instance, it has been reported that Dicer-deleted mice exhibit malformations of the midbrain and cerebellum and failure of neural crest and dopaminergic differentiation (5). In addition, three brain-specific miRNAs (miR-124a, miR-9, and miR-132) have been proposed to regulate the transcription factor REST that mediates neuronal identity (6), and miR-132 seems also to be involved in the control of neuronal morphogenesis by decreasing the GTPase-activating protein, p250GAP (7).…”

Section: Micrornas (Mirnas Mirs)mentioning

confidence: 99%

MicroRNAs-10a and -10b Contribute to Retinoic Acid-induced Differentiation of Neuroblastoma Cells and Target the Alternative Splicing Regulatory Factor SFRS1 (SF2/ASF)

Meseguer

Mudduluru

Escamilla

et al. 2011

Journal of Biological Chemistry

106

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MicroRNAs (miRNAs) are an emerging class of non-coding endogenous RNAs involved in multiple cellular processes, including cell differentiation. Treatment with retinoic acid (RA) results in neural differentiation of neuroblastoma cells. We wanted to elucidate whether miRNAs contribute to the gene expression changes induced by RA in neuroblastoma cells and whether miRNA regulation is involved in the transduction of the RA signal. We show here that RA treatment of SH-SY5Y neuroblastoma cells results in profound changes in the expression pattern of miRNAs. Up to 42 different miRNA species significantly changed their expression (26 up-regulated and 16 down-regulated). Among them, the closely related miR-10a and -10b showed the most prominent expression changes. Induction of miR-10a and -10b by RA also could be detected in LA-N-1 neuroblastoma cells. Loss of function experiments demonstrated that miR-10a and -10b are essential mediators of RA-induced neuroblastoma differentiation and of the associated changes in migration, invasion, and in vivo metastasis. In addition, we found that the SR-family splicing factor SFRS1 (SF2/ASF) is a target for miR-10a -and -10b in HeLa and SH-SY5Y neuroblastoma cells. We show here that changes in miR10a and -10b expression levels may regulate SFRS1-dependent alternative splicing and translational functions. Taken together, our results give support to the idea that miRNA regulation plays a key role in RA-induced neuroblastoma cell differentiation. The discovery of SFRS1 as direct target of miR-10a and -10b supports the emerging functional interaction between two post-transcriptional mechanisms, microRNAs and splicing, in the neuronal differentiation context. MicroRNAs (miRNAs, miRs)5 are an emerging class of small non-coding endogenous RNAs that are involved in multiple biological processes. These tiny regulatory elements are transcribed as primary longer transcripts, which are then processed by Dicer and Drosha complexes into 21-23-nt mature miRNAs. One strand of the mature miRNA is then incorporated into the RNA-induced silencing complex to regulate gene expression by targeting the 3Ј-untranslated region (3Ј-UTR) of mRNAs with consequent translational repression and/or target mRNA degradation. This mode of action demonstrates the great regulatory potential of miRNAs, as a unique mRNA can be targeted by diverse miRNAs, and conversely, each miRNA may have 100s of different target mRNAs (for review, see Refs. 1 and 2).In vertebrates, the highest variety of miRNAs is expressed in the brain than in any other tissue, suggesting an important role in nervous system development (3, 4). Recent studies have revealed the importance of miRNA expression in neural development and differentiation. For instance, it has been reported that Dicer-deleted mice exhibit malformations of the midbrain and cerebellum and failure of neural crest and dopaminergic differentiation (5). In addition, three brain-specific miRNAs (miR-124a, miR-9, and miR-132) have been proposed to regulate the transcription factor R...

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“…In terms of tumor biology therefore, the loss of TFAP2A expression observed in invasive breast cancer is likely to contribute to tumorigenesis irrespective of whether the tumor cells express neural crest cells has recently been shown to abolish AP-2α expression in the sympathetic neurons of the mutant mice. 23 To investigate the role played by TFAP2A in CDKN1A induction in drug-treated MCF10A, cells were transfected with either non-silencing siRNA or the TFAP2A-specifc siRNA and were subsequently treated with either HU or vinblastine, or left untreated as controls. Monitoring mRNA levels revealed that TFAP2A-silencing again significantly reduced CDKN1A expression-both the constitutive, background levels seen in untreated cells but particularly the induced expression in drug-treated cells (see Fig.…”

mentioning

confidence: 99%