Mixl1 is a paired-type

homeobox A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. For instance, mutations in a homeobox may change large-scale anatomical features of the full- ...

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

weighing 27 kDa with 232 amino acids. Mixl1 transcription factor preferentially binds to the

DNA sequence DNA sequencing is the process of determining the nucleic acid sequence – the order of nucleotides in DNA. It includes any method or technology that is used to determine the order of the four bases: adenine, guanine, cytosine, and thymine. Th ...

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.# 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). Mixl1 is transiently expressed in the

primitive streak 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 ...

of the gastrulating embryo, between embryonic day (E) 12 through E.19. Its expression is restricted to embryonic mesoderm precursors.# 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) Also known as: Mix; Mix1; Mild1

Function

Mixl1 plays a role in mesoderm patterning and tissue specification at

gastrulation Gastrulation is the stage in the early embryonic development of most animals, during which the blastula (a single-layered hollow sphere of cells), or in mammals the blastocyst is reorganized into a multilayered structure known as the gastrula. Be ...

. It marks cells destined to be

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical E ...

and

endoderm Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gast ...

. 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.# 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)

Clinical Significance

In mice,

knockout A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, muay thai, mixed martial arts, karate, some forms of taekwondo and other sports involving striking, a ...

of Mixl1 has resulted in

embryonic death Embryo loss (also known as embryo death or embryo resorption) is the death of an embryo at any stage of its development which in humans, is between the second through eighth week after fertilization. Failed development of an embryo often results i ...

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 Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. Symptoms may includ ...

. In humans Mixl1 has been detected in leukemic cells lines from biopsy samples of individuals with high-grade lymphoma.# 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) 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.

Interactions

Mixl1 has been shown to interact with

BMP4 Bone morphogenetic protein 4 is a protein that in humans is encoded by ''BMP4'' gene. BMP4 is found on chromosome 14q22-q23. BMP4 is a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfami ...

References

{{reflist Transcription factors Embryology