Structure, upstream promoter region, and functional domains of a mouse and human Mix paired-like homeobox gene

Sahr, Kenneth E.; Dias, Dora C.; Sánchez, Roberto; Chen, Dongli; Chen, Siming W.; Gudas, Lorraine J.; Baron, Margaret H.

doi:10.1016/s0378-1119(02)00590-5

Cited by 15 publications

(26 citation statements)

References 27 publications

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“…2D, bottom row). The nuclear localization of mMix protein in retinoic acid-induced F9 cells is consistent with its presumed function as a transcription factor and with the ability of recombinant protein to recognize the same DNA sequence as Xenopus Mix.1 and other Q9-type paired class homeodomain proteins (Sahr et al, 2002).…”

Section: Nuclear Localization Of Endogenous MIX Proteinsupporting

confidence: 62%

“…5C). Although mouse Mix is most similar to the Xenopus Mix.1 family member within its homeodomain (Sahr et al, 2002), its activity in the animal cap assay does not mimic the behavior of Xenopus Mix.1 but is similar to that of Xenopus Mix.3/4, mixer, and other family member. These findings suggest a role for mMix in endoderm formation and/or patterning.…”

Section: Mouse MIX Can Induce Endoderm In Xenopus Embryosmentioning

confidence: 91%

“…2B, panel b). Immunostaining of mouse 3T3 cells transfected with an mMix expression construct revealed that mMix, a DNA-binding transcription factor (Sahr et al, 2002), is localized to the nucleus (Fig. 2B, panel c).…”

Section: Nuclear Localization Of Endogenous MIX Proteinmentioning

confidence: 99%

“…However, mMix protein expressed in COS cells (Sahr et al, 2002) paired class homeodomain proteins. In an attempt to define the function of the mouse Mix protein during development, we expressed mMix ectopically in Xenopus embryos.…”

Section: Mouse MIX Can Induce Endoderm In Xenopus Embryosmentioning

confidence: 99%

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Mouse Mix gene is activated early during differentiation of ES and F9 stem cells and induces endoderm in frog embryos

Mohn

Chen

Dias

et al. 2003

Developmental Dynamics

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In frog and zebrafish, the Mix/Bix family of paired type homeodomain proteins play key roles in specification and differentiation of mesendoderm. However, in mouse, only a single Mix gene (mMix) has been identified to date and its function is unknown. We have analyzed the expression of mouse Mix RNA and protein in embryos, embryoid bodies formed from embryonic stem cells and F9 teratocarcinoma cells, as well as several differentiated cell types. Expression in embryoid bodies in culture mirrors that in embryos, where Mix is transcribed transiently in primitive (visceral) endoderm (VE) and in nascent mesoderm. In F9 cells induced by retinoic acid to differentiate to VE, mMix is coordinately expressed with three other endodermal transcription factors, well before AFP, and its protein product is localized to the nucleus. In a subpopulation of nascent mesodermal cells from embryonic stem cell embryoid bodies, mMix is coexpressed with Brachyury. Intriguingly, mMix mRNA is detected in a population (T؉Flk1؉) of cells which may contain hemangioblasts, before the onset of hematopoiesis and activation of hematopoietic markers. In vitro and in vivo, mMix expression in nascent mesoderm is rapidly down-regulated and becomes undetectable in differentiated cell types. In the region of the developing gut, mMix expression is confined to the mesoderm of midand hindgut but is absent from definitive endoderm. Injection of mouse mMix RNA into early frog embryos results in axial truncation of developing tadpoles and, in animal cap assays, mMix alone is sufficient to activate expression of several endodermal (but not mesodermal) markers. Although these observations do not exclude a possible cellautonomous function for mMix in mesendodermal progenitor cells, they do suggest an additional, non-cell autonomous role in nascent mesoderm in the formation and/or patterning of adjacent definitive endoderm. Developmental Dynamics 226:446 -459, 2003.

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Section: Nuclear Localization Of Endogenous MIX Proteinsupporting

confidence: 62%

Section: Mouse MIX Can Induce Endoderm In Xenopus Embryosmentioning

confidence: 91%

Section: Nuclear Localization Of Endogenous MIX Proteinmentioning

confidence: 99%

Section: Mouse MIX Can Induce Endoderm In Xenopus Embryosmentioning

confidence: 99%

See 2 more Smart Citations

Mouse Mix gene is activated early during differentiation of ES and F9 stem cells and induces endoderm in frog embryos

Mohn

Chen

Dias

et al. 2003

Developmental Dynamics

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“…26 Several other Xenopus and zebrafish Mix/Bix genes have been implicated in the formation of endoderm or mesendoderm. 16,[18][19][20]22,24,25,28 Although Mix-related genes have been identified in all eukaryotic species analyzed, 29 only a single Mix gene has been found in mouse, chick, and humans. [29][30][31][32][33] The mouse Mix-like gene (here termed mMix; also known as Mml or Mixl1) is expressed in the posterior visceral endoderm prior to gastrulation and later in the primitive streak and nascent mesoderm.…”

Section: Introductionmentioning

confidence: 99%

Acceleration of mesoderm development and expansion of hematopoietic progenitors in differentiating ES cells by the mouse Mix-like homeodomain transcription factor

Willey

Ayuso-Sacido

Zhang

et al. 2006

Blood

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The cellular and molecular events underlying the formation and differentiation of mesoderm to derivatives such as blood are critical to our understanding of the development and function of many tissues and organ systems. How different mesodermal populations are set aside to form specific lineages is not well understood. Although previous genetic studies in the mouse embryo have pointed to a critical role for the homeobox gene Mixlike (mMix) in gastrulation, its function in mesoderm development remains unclear. IntroductionThe formation of mesoderm is a pivotal process in the normal development of major tissues and organs of the mammalian embryo, including the hematopoietic, cardiovascular, and musculoskeletal systems. During early development, mesoderm is also a crucial component of extraembryonic structures such as the yolk sac, allantois, and placenta. 1,2 Mesoderm begins to form shortly after implantation during a process known as gastrulation. [3][4][5][6] Fate maps suggest that different mesodermal derivatives arise in an orderly manner from patterning of cell populations within distinct posteroanterior regions of the streak. 7,8 The most posterior region of the primitive streak is fated to form the extraembryonic mesoderm, while successively more anterior derivatives give rise to lateral, paraxial, and axial mesoderm. Despite intense effort, the mechanisms underlying the orderly allocation of mesoderm to its various lineages remain obscure. 9 A number of major signaling pathways, including transforming growth factor ␤ (TGF␤), fibroblast growth factor, 10 and Wnt, have been shown to play central roles during gastrulation. 4,6 While the functional relationships among these pathways in the induction and patterning of mesoderm remain to be defined, their activities are likely to be integrated, at least in part, through the downstream activities of nuclear transcription factors. Members of the Mix/Bix family of paired class homeobox genes are direct or indirect targets of the TGF␤ family members Nodal/activin [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25]27 Xenopus Mix.1 (Xmix.1), the founding member of the Mix/Bix family, has been reported to ventralize mesoderm. 26 Several other Xenopus and zebrafish Mix/Bix genes have been implicated in the formation of endoderm or mesendoderm. 16,[18][19][20]22,24,25,28 Although Mix-related genes have been identified in all eukaryotic species analyzed, 29 only a single Mix gene has been found in mouse, chick, and humans. [29][30][31][32][33] The mouse Mix-like gene (here termed mMix; also known as Mml or Mixl1) is expressed in the posterior visceral endoderm prior to gastrulation and later in the primitive streak and nascent mesoderm. [32][33][34] The significance of this gene in gastrulation was revealed by analysis of mMix-deficient mouse embryos, which display numerous mesodermal and endodermal defects and arrest by embryonic day 9.5 (E9.5). 35 For example, the primitive streak is enlarged, a heart tube is absent and, in some mutants, the allantois is abno...

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T-box geneeomesoderminand the homeobox-containing Mix/Bix genemtx2regulate epiboly movements in the zebrafish

et al. 2005

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The T-box gene eomesodermin (eomes) has been implicated in mesoderm specification and patterning in both zebrafish and frog. Here, we describe an additional function for eomes in the control of morphogenesis. Epiboly, the spreading and thinning of an epithelial cell sheet, is a central component of gastrulation in many species; however, despite its importance, little is known about its molecular control. Here, we show that repression of eomes function in the zebrafish embryo dramatically inhibits epiboly movements. We also show that eomes regulates the expression of a zygotic homeobox transcription factor mtx2. Gene knockdown of mtx2 using antisense morpholino oligonucleotides, likewise, leads to an inhibition of epiboly; moreover, we show that knockdown of mtx2 function in the extraembryonic yolk syncytial layer only is sufficient to cause epiboly defects. Thus, we have identified two components in a molecular pathway controlling epiboly and show that interactions between deep layer cells of the embryo proper and extraembryonic tissues contribute in a coordinated manner to different aspects of epiboly movements. Developmental Dynamics 233:105-114, 2005.

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Structure, upstream promoter region, and functional domains of a mouse and human Mix paired-like homeobox gene

Cited by 15 publications

References 27 publications

Mouse Mix gene is activated early during differentiation of ES and F9 stem cells and induces endoderm in frog embryos

Mouse Mix gene is activated early during differentiation of ES and F9 stem cells and induces endoderm in frog embryos

Acceleration of mesoderm development and expansion of hematopoietic progenitors in differentiating ES cells by the mouse Mix-like homeodomain transcription factor

T-box geneeomesoderminand the homeobox-containing Mix/Bix genemtx2regulate epiboly movements in the zebrafish

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