Msx genes define a population of mural cell precursors required for head blood vessel maturation

Lopes, Miguel; Goupille, Olivier; Cloment, Cécile Saint; Lallemand, Yvan; Cumano, Ana; Robert, Benoît

doi:10.1242/dev.063214

Cited by 23 publications

(27 citation statements)

References 60 publications

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“…Msx1-nlacZ mice were described previously (28). The Msx1-CreERT2 allele was generated by introducing the CreERT2 coding sequence (35) (a kind gift of Pierre Chambon, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France) at the initiator ATG site of Msx1 by homologous recombination (30). Additional inducible Cre mouse strains Sp7-tTA-tetO-EGFP::Cre (27), Krt14-CreESR1 (22), and Col2a1-CreERT (26) were obtained from Jackson Laboratories (strains 006361, 005107, and 006774).…”

Section: Methodsmentioning

confidence: 99%

Mouse digit tip regeneration is mediated by fate-restricted progenitor cells

Lehoczky

Robert²,

Tabin³

2011

Proc. Natl. Acad. Sci. U.S.A.

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Regeneration of appendages is frequent among invertebrates as well as some vertebrates. However, in mammals this has been largely relegated to digit tip regeneration, as found in mice and humans. The regenerated structures are formed from a mound of undifferentiated cells called a blastema, found just below the site of amputation. The blastema ultimately gives rise to all of the tissues in the regenerate, excluding the epidermis, and has classically been thought of as a homogenous pool of pluripotent stem cells derived by dedifferentiation of stump tissue, although this has never been directly tested in the context of mammalian digit tip regeneration. Successful digit tip regeneration requires that the level of amputation be within the nail bed and depends on expression of Msx1. Because Msx1 is strongly expressed in the nail bed mesenchyme, it has been proposed that the Msx1-expressing cells represent a pluripotent cell population for the regenerating digit. In this report, we show that Msx1 is dynamically expressed during digit tip regeneration, and it does not mark a pluripotent stem cell population. Moreover, we show that both the ectoderm and mesoderm contain fate-restricted progenitor populations that work in concert to regenerate their own lineages within the digit tip, supporting the hypothesis that the blastema is a heterogeneous pool of progenitor cells.

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Section: Methodsmentioning

confidence: 99%

Mouse digit tip regeneration is mediated by fate-restricted progenitor cells

Lehoczky

Robert²,

Tabin³

2011

Proc. Natl. Acad. Sci. U.S.A.

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193

241

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“…Primary antibodies included antiMath1 (Atoh1; 1:40), anti-Pax7 (1:200), anti-Lhx1/5 (4F2; 1:100), anti-Isl1 (40.2D6; 1:200), all from DSHB; anti-β-galactosidase (MP Biomedicals, 559761; 1:1500); anti-Pax2 (Invitrogen, 71-6000; 1:100); anti-GFP (Invitrogen, A-11122; 1:200); anti-phospho-Smad1/5/8 (Cell Signaling Technology, 951; 1:500); anti-Olig3 (Müller et al, 2005) (1:10,000); and anti-HA (Roche, clone 3F10; 1:100). In situ hybridization on whole-mount embryos (Tajbakhsh et al, 1997) and sections (Lopes et al (2011) were performed as described previously.…”

Section: Immunostaining and In Situ Hybridizationmentioning

confidence: 99%

Msx1 and Msx2 act as essential activators of Atoh1 expression in the murine spinal cord

et al. 2014

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Dorsal spinal neurogenesis is orchestrated by the combined action of signals secreted from the roof plate organizer and a downstream transcriptional cascade. Within this cascade, Msx1 and Msx2, two homeodomain transcription factors (TFs), are induced earlier than bHLH neuralizing TFs. Whereas bHLH TFs have been shown to specify neuronal cell fate, the function of Msx genes remains poorly defined. We describe dramatic alterations of neuronal patterning in Msx1/Msx2 double-mutant mouse embryos. The most dorsal spinal progenitor pool fails to express the bHLH neuralizing TF Atoh1, which results in a lack of Lhx2-positive and Barhl2-positive dI1 interneurons. Neurog1 and Ascl1 expression territories are dorsalized, leading to ectopic dorsal differentiation of dI2 and dI3 interneurons. In proportion, the amount of Neurog1-expressing progenitors appears unaffected, whereas the number of Ascl1-positive cells is increased. These defects occur while BMP signaling is still active in the Msx1/ Msx2 mutant embryos. Cell lineage analysis and co-immunolabeling demonstrate that Atoh1-positive cells derive from progenitors expressing both Msx1 and Msx2. In vitro, Msx1 and Msx2 proteins activate Atoh1 transcription by specifically interacting with several homeodomain binding sites in the Atoh1 3′ enhancer. In vivo, Msx1 and Msx2 are required for Atoh1 3′ enhancer activity and ChIP experiments confirm Msx1 binding to this regulatory sequence. These data support a novel function of Msx1 and Msx2 as transcriptional activators. Our study provides new insights into the transcriptional control of spinal cord patterning by BMP signaling, with Msx1 and Msx2 acting upstream of Atoh1.

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“…Single or double homozygous mutant embryos were obtained by NMRI Msx1 +/-Msx2 +/- (Bensoussan et al, 2008;Houzelstein et al, 1997) intercrosses. Production of Msx1creERT2 mice by homologous recombination in embryonic stem (ES) cells is described elsewhere (Lopes et al, 2011). The targeted reporter allele was ROSAmT/mG as previously described (Muzumdar et al, 2007).…”

Section: Mice and Embryosmentioning

confidence: 99%

Msx1 and Msx2 promote meiosis initiation

et al. 2011

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SUMMARYThe mechanisms regulating germ line sex determination and meiosis initiation are poorly understood. Here, we provide evidence for the involvement of homeobox Msx transcription factors in foetal meiosis initiation in mammalian germ cells. Upon meiosis initiation, Msx1 and Msx2 genes are strongly expressed in the foetal ovary, possibly stimulated by soluble factors found there: bone morphogenetic proteins Bmp2 and Bmp4, and retinoic acid. Analysis of Msx1/Msx2 double mutant embryos revealed a majority of undifferentiated germ cells remaining in the ovary and, importantly, a decrease in the number of meiotic cells. In vivo, the Msx1/Msx2 double-null mutation prevented full activation of Stra8, a gene required for meiosis. In F9 cells, Msx1 can bind to Stra8 regulatory sequences and Msx1 overexpression stimulates Stra8 transcription. Collectively, our data demonstrate for the first time that some homeobox genes are required for meiosis initiation in the female germ line.

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Msx genes define a population of mural cell precursors required for head blood vessel maturation

Cited by 23 publications

References 60 publications

Mouse digit tip regeneration is mediated by fate-restricted progenitor cells

Mouse digit tip regeneration is mediated by fate-restricted progenitor cells

Msx1 and Msx2 act as essential activators of Atoh1 expression in the murine spinal cord

Msx1 and Msx2 promote meiosis initiation

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