What is Meis2 (or MEIS2)?

MEIS2 is a gene that helps developing cells work out what they’re going to be. It does that by controlling which other genes get switched on and which stay quiet, which puts it at the making of the brain, the eyes, the face, the heart and a good deal else besides. It also shapes the production and specialization of certain neurons. Rare harmful variants in the gene, though, can cause a developmental disorder marked by intellectual disability, speech and developmental delays, heart defects and abnormalities of the palate. 1

MEIS2 is not a disease, and it isn’t a signaling pathway. It’s a protein-coding gene that produces a transcription factor, a protein that helps cells read the instructions written in DNA. It’s also what puts MEIS2 at the heart of some very complicated developmental decisions.

MEIS2 At A Glance

• Official human gene name: Meis homeobox 2
• Gene symbol: MEIS2 in humans
• Chromosome location: 15q14
• Gene type: Protein-coding
• Protein: Homeobox protein Meis2
• Protein family: TALE homeobox transcription factors
• Major biological roles under study: Cell fate specification, neurogenesis, brain regionalization, retinal development, craniofacial development, and heart development
• Human disease association: Pathogenic loss of normal MEIS2 function is associated with a rare developmental disorder involving intellectual disability, palatal abnormalities, and congenital heart defects. 1

Why Is It Sometimes Written MEIS2 And Sometimes Meis2?

Same gene. The spelling just follows naming rules that differ from species to species.

In humans, the official gene symbol is MEIS2, all capitals. The human protein is written MEIS2 too, minus the italics.

In mice, the matching gene is Meis2, first letter only. The mouse protein is still MEIS2.

Which is why human genetics papers tend to say MEIS2, while developmental biology papers, so many of which work on mice, say Meis2. Frogs, zebrafish and the rest have their own conventions layered on top of that.

The official human name for the gene is Meis homeobox 2. Older papers may spell MEIS2 out as “myeloid ecotropic viral integration site 2,” or reach for an old alias like MRG1. Those names record how the gene was found. They say nothing about what it does.

What Does the MEIS2 Protein Do?

MEIS2 helps a developing cell decide what it should become, and it does that by helping control which genes are turned on and which stay off.

Scientists call MEIS2 a transcription factor for exactly that reason. It belongs to a group called homeobox proteins, which recognize specific places in DNA and help cells choose which genetic instructions to follow.

Within that group, MEIS2 sits in a smaller family known as the TALE proteins, and it carries a region called the MEINOX domain that lets it connect with other proteins that control genes. 2

The teamwork matters, because MEIS2 rarely acts alone. It can work with proteins from the PBX, HOX, PAX and DLX families, and different combinations turn different genes on or off.

So MEIS2 doesn’t do quite the same thing in every cell. What it does depends on the other proteins nearby, on which parts of the DNA the cell can reach, and on how far along the cell already is.

Put plainly, MEIS2 helps a developing cell answer a handful of basic questions. Where am I in the body? What kind of cell should I become? Which genes do I turn on, and which do I leave alone?

The human MEIS2 protein is listed in UniProt under accession O14770. And the MEIS2 gene can make several slightly different versions of the protein.

MEIS2 Helps Cells Acquire Their Identity

Much of what scientists know about MEIS2 has come from watching animals develop.

Early on, many cells are still very much alike. Over time they have to become nerve cells, muscle cells, skin cells and everything else, and transcription factors are what guide them there, turning genes on and off at the right time and in the right place. MEIS2 is one of those guides.

A 2025 study in Frontiers in Neuroanatomy mapped where the Meis2 gene was switched on as the frog Xenopus laevis developed. Researchers found it across the growing nervous system, including several regions of the brain. 2

Meis2 has been tracked in mammals, fish and other animals with backbones as well. The exact pattern isn’t the same in every species. But it often shows up just as the brain is being carved into regions and young nerve cells are starting to take on specialized jobs.

Because that pattern recurs in so many different animals, researchers reckon MEIS2 has been helping shape developing nervous systems for hundreds of millions of years.

MEIS2 and the Developing Brain

The developing brain is where you can watch MEIS2 help young cells choose what they’ll become.

Early in brain development, some nerve cells form in temporary areas called the ganglionic eminences. Cells there can develop into several kinds of GABAergic neurons, nerve cells that help control activity in the brain. Some become projection neurons, which send signals over longer distances. Others become interneurons, wiring up their immediate neighbors.

A 2024 study in Nature Neuroscience set out to work out how a cell picks between those fates. The team used several modern genetic tools to track developing cells and read which genes were active in them, and found that MEIS2 pushes some young cells toward becoming GABAergic projection neurons. Disrupt the Meis2 gene and fewer projection neurons developed, while some types of interneuron became more common. 3

MEIS2 does this partly through stretches of DNA called enhancers, which help control when nearby genes are switched on. It worked alongside another transcription factor, DLX5, at enhancers linked to projection-neuron genes; together, the pair switched those regions on more strongly than either could manage alone. 3

Another transcription factor, LHX6, could work against parts of this process. Which is a reminder that cell development is rarely controlled by a single gene. A cell’s identity emerges instead from several proteins working together, and sometimes working against one another.

MEIS2 Also Plays a Role in Adult Neurogenesis

MEIS2 doesn’t clock off once the brain has finished its early development.

A 2014 study in Development followed the young nerve cells that help make new neurons in the adult mouse brain. These cells travel from one part of the brain to the olfactory bulb, an area involved in smell, and the Meis2 gene was highly active in them while they moved. 4

Interfere with Meis activity, and the young cells had trouble becoming neurons at all. MEIS2 also helped some of them develop into a special type of nerve cell in the olfactory bulb, one that uses the chemical dopamine.

The researchers traced its influence to several genes involved in the process, Dcx and Th among them, and found evidence that MEIS2 works with other transcription factors including PAX6 and DLX2. 4

So MEIS2 is not simply present while new neurons form. It takes an active hand in switching on the genetic program that helps young cells become working nerve cells.

MEIS2 Helps Organize the Developing Retina

The retina, the light-sensitive tissue at the back of the eye, is another place MEIS2 leaves its mark.

A 2021 study in Proceedings of the National Academy of Sciences looked at Meis1 and Meis2 together in the developing mouse eye, and the two genes turn out to cover for each other to some extent. When researchers removed both, young retinal cells lost some of their normal identity, and the borders between different parts of the developing eye grew less organized. 5

Meis proteins, the researchers found, keep young retinal cells on the path toward becoming retinal tissue while blocking the alternative routes. Removing Meis1 and Meis2 also shifted the activity of genes involved in cell signaling, nerve-cell development and retinal growth. 5

Then came a different question. Could extra MEIS1 or MEIS2 make older retinal cells behave more like younger ones?

A 2025 study in Scientific Reports found that extra MEIS2 did change the activity of important developmental genes, and sped up some steps in nerve-cell development. But it could not fully turn later-stage retinal cells back into younger ones, nor coax them into producing the early retinal cell types the researchers wanted. 6

MEIS2 can help shape what a developing cell is able to become. It’s not a reset button that wipes away the cell’s past.

Why Are MEIS2 Variants Associated With Human Disease?

Some of the strongest evidence for how much MEIS2 matters comes from people who carry rare changes, or variants, in the MEIS2 gene.

Most of us have two copies of MEIS2, one from each parent. If one copy doesn’t work properly, the body may not make enough normal MEIS2 protein to go round during development, and the result can be a developmental disorder. Common features include developmental delays, intellectual disability, serious speech problems in some people, cleft palate, and heart defects present at birth. 7

The effects can differ greatly from one person to the next. Which makes sense, given that MEIS2 helps guide the development of several parts of the body and can act at different stages.

The case for MEIS2-related disease was built up piece by piece. First came people missing a section of chromosome 15 that contains MEIS2. Later came people with changes in the MEIS2 gene itself. Because MEIS2 kept turning up, researchers concluded that a single working copy may not supply enough for normal development. 7

A 2021 report in the American Journal of Medical Genetics Part A described a child with a new MEIS2 variant called p.Arg333Lys. She had intellectual disability, major developmental delays, a cleft palate, and a heart defect present at birth. 7

That variant alters one part of the MEIS2 protein that helps it interact with DNA. The 2024 Nature Neuroscience study tested the altered form in the lab and found it much less effective than normal MEIS2 at working with DLX5 to switch on certain DNA control regions involved in nerve-cell development. 3

Which gives scientists a possible link between a change in the MEIS2 gene and trouble in the way developing cells turn genes on and off. But it does not mean that changes in one type of brain cell explain every feature of MEIS2-related disease. MEIS2 works in many tissues, so the disorder likely reflects changes in the development of several parts of the body.

Why Can One Gene Affect the Brain, Heart, and Palate?

Genes that guide early development tend to get used all over the body. That is why a change in one of them can ripple out through several organs at once.

MEIS2 helps control development in the brain, face, palate and heart, but not by doing the same job in every tissue. Its effects depend on the other proteins working with it in each type of cell.

A developing brain cell and a developing facial cell may both reach for MEIS2 and put it to entirely different uses, because each has a different set of genes and regulatory proteins available to it.

Think of MEIS2 as part of a shared set of instructions. Different cells read those instructions in different ways.

Which is why harmful changes in MEIS2 rarely stay in one lane. A person may have intellectual disability, problems with the palate, heart defects present at birth, and differences in facial development, rather than a condition limited to just one organ. 7

Is MEIS2 a Cancer Gene?

Scientists are studying MEIS2 in cancer too. The picture there is less clear than in normal development.

MEIS2 helps control which genes are turned on, how cells grow and what kind of cells they become, so it is reasonable to expect changes in its activity to affect how cancer cells behave. But MEIS2 does not simply act as a “cancer gene” that always helps or always stops tumors. Its effects may differ from one kind of cancer to another.

Prostate cancer offers one example. A 2025 study in The Prostate looked at MEIS2, cancer-cell metabolism and CD8+ T cells, the immune cells that can attack tumor cells. 8

Levels of MEIS2 were lower in prostate cancer. Tumors carrying more of it also tended to have more CD8+ T cells. In laboratory experiments, raising MEIS2 levels helped those T cells kill cancer cells more effectively; lowering MEIS2 changed how the cancer cells produced energy, and was linked to weaker CD8+ T cell activity. 8

The suggestion is that MEIS2 may sit somewhere between a tumor’s metabolism and the immune system’s ability to fight it. Early days, though. MEIS2 is not an approved cancer treatment target, and much more research is needed before anyone knows whether these findings could lead to new treatments.

What Makes MEIS2 Scientifically Interesting?

MEIS2 keeps turning up because it sits at the junction of several big questions about how cells develop and behave.

Researchers who study development want to know how cells use genetic instructions to build tissues and organs. Brain scientists want to understand how near-identical young cells end up as different kinds of neuron. Geneticists are working out why changes in MEIS2 can reach the brain, heart, palate and face. Others want to know whether proteins like MEIS2 can change what older cells are able to become. And cancer scientists are asking whether MEIS2 affects tumor growth, energy use and the immune response.

The common thread is that MEIS2 helps cells decide how to use the information already stored in their DNA.

Studies of MEIS2 and the DLX proteins show how that works. MEIS2 does not simply turn on the same genes wherever it appears. Its effects depend on which other proteins are present, and which parts of the DNA are available for those proteins to use.3

Better, then, to think of MEIS2 as a partner than as a simple on-off switch. What it does depends on where the cell is, what stage of development it has reached, which genes are available, and who else is in the room.

Is MEIS2 a Gene or a Protein?

Both, depending on the context.

The MEIS2 gene is a stretch of DNA carrying the instructions for making the MEIS2 protein. Cells can process those instructions in slightly different ways, which is how one gene yields several versions of the protein.

The MEIS2 protein is the transcription factor. It can enter the cell nucleus, bind to DNA, and work with other proteins to help turn genes on or off.

In scientific writing, the gene name MEIS2 is usually italicized while the protein name MEIS2 is not. In news stories, databases and search results, though, “MEIS2” tends to get used for both.

What Does MEIS2 Stand For?

Officially, Meis homeobox 2.

Older research papers may use names such as “myeloid ecotropic viral integration site 2.” The gene has also been called MRG1. Today, resources such as NCBI Gene list the human gene as MEIS2.

“Meis homeobox 2” is the more useful name, because it flags the thing that matters: MEIS2 makes a homeobox protein, one that can recognize certain parts of DNA and help control gene activity.

Is MEIS2 Associated With Intellectual Disability?

Yes. Rare harmful changes in the MEIS2 gene can cause a developmental disorder in which intellectual disability or developmental delay is common.

Some people with these variants also have major speech delays, cleft palate or other problems with the palate, and heart defects present at birth. 7

That isn’t the same as saying MEIS2 explains common differences in learning, speech, behavior or intelligence. It doesn’t. The medical cases involve rare genetic changes that greatly reduce or disrupt the gene’s normal function.

Does MEIS2 Control Neurogenesis?

MEIS2 helps control neurogenesis, the process of making new nerve cells.

Work in animals and in cultured cells shows MEIS2 steering young cells toward certain kinds of neuron, in the adult mouse olfactory bulb, in the developing brain, and in the developing retina. 3, 4, 5

None of which means MEIS2 could be used to regrow the human brain. Much of the evidence comes from mice, from other animals, or from cells grown in the laboratory, and the distance between that and a safe treatment for people is considerable.

The Bottom Line

MEIS2 is a gene, and the protein it makes helps developing cells decide what they will become.

It works by helping control which genes are turned on or off. But MEIS2 does not do the same job everywhere: its effects hang on the type of cell, the stage of development, and the other proteins working with it.

In the brain, MEIS2 helps young nerve cells sort themselves into different types of neuron. In the eye, Meis proteins help organize the developing retina.3, 4, 5 In other tissues it has important roles during development too.

Which is why rare harmful changes in MEIS2 can affect several parts of the body at once. They can cause intellectual disability, developmental and speech delays, problems with the palate, and heart defects present at birth. 7

Regenerative medicine and cancer are the newer frontiers, and that work is still developing.

The settled part is the interesting part. MEIS2 is part of the system that helps a developing cell answer one of biology’s most important questions: What kind of cell should I become?

References

1. NCBI Gene: MEIS2, Meis homeobox 2. National Center for Biotechnology Information.

2. Morona R, Martinez A, Moreno N. Developmental and adult expression of the Meis2 transcription factor in the central nervous system of Xenopus laevis: a developmental and evolutive analysis. Frontiers in Neuroanatomy. 2025;19. doi:10.3389/fnana.2025.1677413.

3. Dvoretskova E, Ho MC, Kittke V, et al. Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development. Nature Neuroscience. 2024;27:862-872. doi:10.1038/s41593-024-01611-9.

4. Agoston Z, Heine P, Brill MS, et al. Meis2 is a Pax6 co-factor in neurogenesis and dopaminergic periglomerular fate specification in the adult olfactory bulb. Development. 2014;141(1):28-38. doi:10.1242/dev.097295.

5. Dupacova N, Antosova B, Paces J, Kozmik Z. Meis homeobox genes control progenitor competence in the retina. Proceedings of the National Academy of Sciences. 2021;118(12):e2013136118. doi:10.1073/pnas.2013136118.

6. Leavey P, Jiang L, Pannullo N, Santiago C, Blackshaw S. Overexpression of Meis factors in late-stage retinal progenitors yields complex effects on temporal patterning and neurogenesis. Scientific Reports. Published online December 3, 2025. doi:10.1038/s41598-025-31061-7.

7. Gangfuss A, Yigit G, Altmuller J, et al. Intellectual disability associated with craniofacial dysmorphism, cleft palate, and congenital heart defect due to a de novo MEIS2 mutation: A clinical longitudinal study. American Journal of Medical Genetics Part A. 2021. doi:10.1002/ajmg.a.62070.

8. Han D, Jiang C, Liu H, et al. MEIS2 Modulates Oxidative Phosphorylation and ROS Generation to Affect CD8+ T Cell Antitumor Immunity in Prostate Cancer. The Prostate. 2025. doi:10.1002/pros.70051.