MIXL1

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Mixl1 is a paired-type homeobox transcription factor weighing 27 kDa with 232 amino acids. [1] Mixl1 transcription factor preferentially binds to the DNA sequence TAAT on the Mix gene. Mixl1 is part of the Mix/Bix family of transcription factors, with Mixl1 being the only member identified in humans. The Xenopus Mix gene and human Mix genese are homologues. Mixl1 is functionally similar to the Xenopus Mix.1. [2]

Contents

Mixl1 is transiently expressed in the primitive streak of the gastrulating embryo, between embryonic day (E) 12 through E.19. Its expression is restricted to embryonic mesoderm precursors. [3]

Also known as: Mix; Mix1; Mild1

Function

Mixl1 plays a role in mesoderm patterning and tissue specification at gastrulation. It marks cells destined to be mesoderm and endoderm. Mixl1 expression is required for both mesoderm development and hematopoiesis. Mixl1 homologues are also a necessary intermediate for BMP4-induced ventral mesoderm patterning and differentiating ES cells. [4]

Clinical Significance

In mice, knockout of Mixl1 has resulted in embryonic death at E.8.5 due abnormalities in axial morphogenesis and a disruption of definitive endoderm. Overexpression of Mixl1 resulted in impaired hematopoietic differentiation which results in acute myeloid leukemia. In humans Mixl1 has been detected in leukemic cells lines from biopsy samples of individuals with high-grade lymphoma. [5]

Observed Mixl1-null mutants resulted in embryonic arrest at the early somite stage. These mutants had a thick primitive streak, abnormal head folds, absence of heart tube and gut, and enlarged midline tissue mass that replaced the notochord. [3]

Interactions

Mixl1 has been shown to interact with BMP4.

Related Research Articles

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Gastrulation is the stage in the early embryonic development of most animals, during which the blastula, or in mammals the blastocyst is reorganized into a multilayered structure known as the gastrula. Before gastrulation, the embryo is a continuous epithelial sheet of cells; by the end of gastrulation, the embryo has begun differentiation to establish distinct cell lineages, set up the basic axes of the body, and internalized one or more cell types including the prospective gut.

<span class="mw-page-title-main">Neurula</span> Embryo at the early stage of development in which neurulation occurs

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<span class="mw-page-title-main">Primitive streak</span> Structure in early amniote embryogenesis

The primitive streak is a structure that forms in the early embryo in amniotes. In amphibians the equivalent structure is the blastopore. During early embryonic development, the embryonic disc becomes oval shaped, and then pear-shaped with the broad end towards the anterior, and the narrower region projected to the posterior. The primitive streak forms a longitudinal midline structure in the narrower posterior (caudal) region of the developing embryo on its dorsal side. At first formation the primitive streak extends for half the length of the embryo. In the human embryo this appears by stage 6, about 17 days.

<span class="mw-page-title-main">Bone morphogenetic protein 4</span> Gene of the species Homo sapiens

Bone morphogenetic protein 4 is a protein that in humans is encoded by BMP4 gene. BMP4 is found on chromosome 14q22-q23.

Chordin is a protein with a prominent role in dorsal–ventral patterning during early embryonic development. In humans it is encoded for by the CHRD gene.

<span class="mw-page-title-main">Eye development</span> Formation of the eye during embryonic development

Eye formation in the human embryo begins at approximately three weeks into embryonic development and continues through the tenth week. Cells from both the mesodermal and the ectodermal tissues contribute to the formation of the eye. Specifically, the eye is derived from the neuroepithelium, surface ectoderm, and the extracellular mesenchyme which consists of both the neural crest and mesoderm.

In the field of developmental biology, regional differentiation is the process by which different areas are identified in the development of the early embryo. The process by which the cells become specified differs between organisms.

<span class="mw-page-title-main">Cerberus (protein)</span> Protein-coding gene in the species Homo sapiens

Cerberus is a protein that in humans is encoded by the CER1 gene. Cerberus is a signaling molecule which contributes to the formation of the head, heart and left-right asymmetry of internal organs. This gene varies slightly from species to species but its overall functions seem to be similar.

<span class="mw-page-title-main">HOXA9</span> Protein-coding gene in humans

Homeobox protein Hox-A9 is a protein that in humans is encoded by the HOXA9 gene.

<span class="mw-page-title-main">Homeobox A10</span> Protein-coding gene in humans

Homeobox protein Hox-A10 is a protein that in humans is encoded by the HOXA10 gene.

<span class="mw-page-title-main">HOXB6</span> Protein-coding gene in the species Homo sapiens

Homeobox protein Hox-B6 is a protein that in humans is encoded by the HOXB6 gene.

<i>HLX</i> (gene) Protein-coding gene in the species Homo sapiens

Homeobox Protein HB24 is a protein that in humans is encoded by the HLX gene.

<span class="mw-page-title-main">Nodal homolog</span> Mammalian protein found in Homo sapiens

Nodal homolog is a secretory protein that in humans is encoded by the NODAL gene which is located on chromosome 10q22.1. It belongs to the transforming growth factor beta (TGF-β) superfamily. Like many other members of this superfamily it is involved in cell differentiation in early embryogenesis, playing a key role in signal transfer from the primitive node, in the anterior primitive streak, to lateral plate mesoderm (LPM).

<span class="mw-page-title-main">Homeobox protein goosecoid</span> Protein-coding gene in the species Homo sapiens

Homeobox protein goosecoid(GSC) is a homeobox protein that is encoded in humans by the GSC gene. Like other homeobox proteins, goosecoid functions as a transcription factor involved in morphogenesis. In Xenopus, GSC is thought to play a crucial role in the phenomenon of the Spemann-Mangold organizer. Through lineage tracing and timelapse microscopy, the effects of GSC on neighboring cell fates could be observed. In an experiment that injected cells with GSC and observed the effects of uninjected cells, GSC recruited neighboring uninjected cells in the dorsal blastopore lip of the Xenopus gastrula to form a twinned dorsal axis, suggesting that the goosecoid protein plays a role in the regulation and migration of cells during gastrulation.

The Nodal signaling pathway is a signal transduction pathway important in regional and cellular differentiation during embryonic development.

<span class="mw-page-title-main">Ectoderm specification</span> Stage in embryonic development

In Xenopus laevis, the specification of the three germ layers occurs at the blastula stage. Great efforts have been made to determine the factors that specify the endoderm and mesoderm. On the other hand, only a few examples of genes that are required for ectoderm specification have been described in the last decade. The first molecule identified to be required for the specification of ectoderm was the ubiquitin ligase Ectodermin ; later, it was found that the deubiquitinating enzyme, FAM/USP9x, is able to overcome the effects of ubiquitination made by Ectodermin in Smad4. Two transcription factors have been proposed to control gene expression of ectodermal specific genes: POU91/Oct3/4 and FoxIe1/Xema. A new factor specific for the ectoderm, XFDL156, has shown to be essential for suppression of mesoderm differentiation from pluripotent cells.

tinman, or tin is an Nk2-homeobox containing transcription factor first isolated in Drosophila flies. The human homolog is the Nkx2-5 gene. tinman is expressed in the precardiac mesoderm and is responsible for the differentiation, proliferation, and specification of cardiac progenitor cells. This gene is named after the character Tin Woodman who lacks a heart, as flies with nonfunctional tinman genes have cardiac deformities.

Lim-1 is a homeobox transcription factor. This transcription factor is found in adults in the cerebellum, kidneys, and cerebrum, but plays a larger role in development of the fetal head and the female reproductive tract during gestation. During development it is found in the anterior visceral endoderm, is in tissues formed by the primitive streak, and is required in both tissues for head formation. Lim1 is a member of the LIM homeobox gene and encodes a 406 amino acid protein.

<span class="mw-page-title-main">Musashi-2</span> Protein-coding gene in the species Homo sapiens

Musashi-2, also known as Musashi RNA binding protein 2, is a protein that in humans is encoded by the MSI2 gene. Like its homologue musashi-1 (MSI1), it is an RNA-binding protein involved in stemness.

References

  1. ↑
    1. "Homeobox Protein MIXL1 - MIXL1 - Homo sapiens (Human)." Homeobox Protein MIXL1 - MIXL1 - Homo sapiens (Human). N.p., 16 Apr. 2014. Web. 15 Apr. 2014.
  2. ↑
    1. Cloning, expression analysis, and chromosomal localization of murine and human homologues of a Xenopus Mix gene. Robb, L., Hartley, L., Begley, C. G., Brodnicki, T. C., Copeland, N. G., Gilbert, D. J., Jenkins, N. A. and Elefanty, A. G. Dec. Dyn. 219, 497-504 (2000) PMID   11084649.
  3. 1 2
    1. Mixl1 is required for axial mesendoderm morphogenesis and patterning in the murine embryo. Hart, A.H., Hartley, L., Sourris, K., Stadler, E.S., Li, R., Stanley, E.G., Tam, P.P., Elefanty, A.G., Robb, L. Development (2002) PMID   12117810
  4. ↑
    1. The primitive streak gene Mixl1 is required for efficient haematopoiesis and BMP4-induced ventral mesoderm patterning in differentiating ES cells. Ng, E.S., Azzola, L., Sourris, K., Robb, L., Stanley, E.G., Elefanty, A.G. Development (2005) PMID   15673572
  5. ↑
    1. Enforced expression of the homeobox gene Mixl1 impairs hematopoietic differentiation and results in acute myeloid leukemia. Glaser, S., Metcalf, D., Wu, L., Hart, A.H., Dirago, L., Mifsud, S., D'Amico, A., Dagger, S., Campo, C., Chan, A.C., Izon, D.J., Robb, L. Proc. Natl. Acad. Sci. U.S.A. (2006) PMID   17060613
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