Two enhancer domains control early aspects of the complex expression pattern of Msx1

MacKenzie, Alasdair; Purdie, Lorna A.; Davidson, Duncan; Collinson, Martin; Hill, Robert E.

doi:10.1016/s0925-4773(96)00646-6

Cited by 45 publications

(38 citation statements)

References 29 publications

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“…6A), and the DE drives gene expression specifically in orofacial primordia (MacKenzie et al, 1997). We identified a Tcf/Lef-binding site in the DE region of the Msx1 promoter (Fig.…”

Section: Msx1 and Msx2 But Not Bmp4 Were Positively Targeted By The Lmentioning

confidence: 93%

Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion

et al. 2009

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Neither the mechanisms that govern lip morphogenesis nor the cause of cleft lip are well understood. We report that genetic inactivation of Lrp6, a co-receptor of the Wnt/β-catenin signaling pathway, leads to cleft lip with cleft palate. The activity of a Wnt signaling reporter is blocked in the orofacial primordia by Lrp6 deletion in mice. The morphological dynamic that is required for normal lip formation and fusion is disrupted in these mutants. The expression of the homeobox genes Msx1 and Msx2 is dramatically reduced in the mutants, which prevents the outgrowth of orofacial primordia, especially in the fusion site. We further demonstrate that Msx1 and Msx2 (but not their potential regulator Bmp4) are the downstream targets of the Wnt/β-catenin signaling pathway during lip formation and fusion. By contrast, a `fusion-resistant'gene, Raldh3 (also known as Aldh1a3), that encodes a retinoic acid-synthesizing enzyme is ectopically expressed in the upper lip primordia of Lrp6-deficient embryos, indicating a region-specific role of the Wnt/β-catenin signaling pathway in repressing retinoic acid signaling. Thus, the Lrp6-mediated Wnt signaling pathway is required for lip development by orchestrating two distinctively different morphogenetic movements.

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“…6A), and the DE drives gene expression specifically in orofacial primordia (MacKenzie et al, 1997). We identified a Tcf/Lef-binding site in the DE region of the Msx1 promoter (Fig.…”

Section: Msx1 and Msx2 But Not Bmp4 Were Positively Targeted By The Lmentioning

confidence: 93%

Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion

et al. 2009

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“…In mice, an AP-2 homolog is expressed in the urogenital epithelium (albeit in both sexes) and at least one AP-2 homolog shows sexually dimorphic expression (albeit in the brain) (Coelho et al, 2005). The mouse Dr homolog Msx1 is expressed in the genital ridge (MacKenzie et al, 1997) and Msx2 functions in female reproductive tract development (Yin et al, 2006). In chick embryos, Msx1 and Msx2 are expressed male specifically in the Müllerian ducts (Ha et al, 2008).…”

Section: Research Articlementioning

confidence: 99%

The female-specific Doublesex isoform regulates pleiotropic transcription factors to pattern genital development inDrosophila

et al. 2011

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Regulatory networks driving morphogenesis of animal genitalia must integrate sexual identity and positional information. Although the genetic hierarchy that controls somatic sexual identity in the fly Drosophila melanogaster is well understood, there are very few cases in which the mechanism by which it controls tissue-specific gene activity is known. In flies, the sex-determination hierarchy terminates in the doublesex (dsx) gene, which produces sex-specific transcription factors via alternative splicing of its transcripts. To identify sex-specifically expressed genes downstream of dsx that drive the sexually dimorphic development of the genitalia, we performed genome-wide transcriptional profiling of dissected genital imaginal discs of each sex at three time points during early morphogenesis. Using a stringent statistical threshold, we identified 23 genes that have sex-differential transcript levels at all three time points, of which 13 encode transcription factors, a significant enrichment. We focus here on three sex-specifically expressed transcription factors encoded by lozenge (lz), Drop (Dr) and AP-2. We show that, in female genital discs, Dsx activates lz and represses Dr and AP-2. We further show that the regulation of Dr by Dsx mediates the previously identified expression of the fibroblast growth factor Branchless in male genital discs. The phenotypes we observe upon loss of lz or Dr function in genital discs explain the presence or absence of particular structures in dsx mutant flies and thereby clarify previously puzzling observations. Our time course of expression data also lays the foundation for elucidating the regulatory networks downstream of the sex-specifically deployed transcription factors.

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“…A transgene containing 5 kb upstream fragment of Msx1 gene (MacKenzie et al, 1997;Takahashi et al, 1997), EGFP cDNA and SV40 polyadenylation sequence was used to generate pMsx1-EGFP mice. Mice were analyzed at E10.0 (n=5), E10.5 (n=4) and E11.5 (n=4).…”

Section: Generation Of Pmsx1-egfp Micementioning

confidence: 99%

Hes genes and neurogenin regulate non-neural versus neural fate specification in the dorsal telencephalic midline

et al. 2008

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The choroid plexus in the brain is unique because it is a non-neural secretory tissue. It secretes the cerebrospinal fluid and functions as a blood-brain barrier, but the precise mechanism of specification of this non-neural tissue has not yet been determined. Using mouse embryos and lineage-tracing analysis, we found that the prospective choroid plexus region initially gives rise to Cajal-Retzius cells, specialized neurons that guide neuronal migration. Inactivation of the bHLH repressor genes Hes1, Hes3 and Hes5 upregulated expression of the proneural gene neurogenin 2 (Ngn2) and prematurely depleted Bmp-expressing progenitor cells, leading to enhanced formation of Cajal-Retzius cells and complete loss of choroid plexus epithelial cells. Overexpression of Ngn2 had similar effects. These data indicate that Hes genes promote specification of the fate of choroid plexus epithelial cells rather than the fate of Cajal-Retzius cells by antagonizing Ngn2 in the dorsal telencephalic midline region, and thus this study has identified a novel role for bHLH genes in the process of deciding which cells will have a non-neural versus a neural fate.

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Two enhancer domains control early aspects of the complex expression pattern of Msx1

Cited by 45 publications

References 29 publications

Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion

Lrp6-mediated canonical Wnt signaling is required for lip formation and fusion

The female-specific Doublesex isoform regulates pleiotropic transcription factors to pattern genital development inDrosophila

Hes genes and neurogenin regulate non-neural versus neural fate specification in the dorsal telencephalic midline

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