Zinc finger E-box-binding homeobox 2 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''ZEB2''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
The ZEB2 protein is a
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 f ...
that plays a role in the
transforming growth factor β
Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes three different mammalian isoforms (TGF-β 1 to 3, HGNC symbols TGFB1, TGFB2, TGFB3) and many other sign ...
(TGFβ) signaling pathways that are essential during early fetal development.
Function
ZEB2 (previously also known as SMADIP1, SIP1) and its mammalian paralog
ZEB1 belongs to the Zeb family within the ZF (zinc finger) class of homeodomain transcription factors. ZEB2 protein has 8 zinc fingers and 1 homeodomain.
The structure of the homeodomain shown on the right.
ZEB2 interacts with receptor-mediated, activated full-length
SMADs.
The activation of TGFβ receptors brings about the phosphorylation of intracellular effector molecules, R-SMADs. ZEB2 is an R-SMAD-binding protein and acts as a transcriptional corepressor. It is involved in the timing of the conversion of
neuroepithelial cell Neuroepithelial cells, or neuroectodermal cells, form the wall of the closed neural tube in early embryonic development. The neuroepithelial cells span the thickness of the tube's wall, connecting with the pial surface and with the ventricular or ...
s into
radial glia
Radial glial cells, or radial glial progenitor cells (RGPs), are bipolar-shaped progenitor cells that are responsible for producing all of the neurons in the cerebral cortex. RGPs also produce certain lineages of glia, including astrocytes and ol ...
l cells in early development, a mechanism thought to allow for the large differences in
brain size
The size of the brain is a frequent topic of study within the fields of anatomy, biological anthropology, animal science and evolution. Brain size is sometimes measured by weight and sometimes by volume (via MRI scans or by skull volume). Neur ...
between humans and other mammals.
ZEB2 transcripts are found in tissues differentiated from the
neural crest
Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...
such as the
cranial nerve ganglia
In neuroanatomy, the cranial nerve ganglia are ganglia of certain cranial nerves. They can be parasympathetic or sensory. All cranial nerve ganglia are bilateral.
Parasympathetic
The four cranial parasympathetic ganglia are:
* ciliary ganglio ...
,
dorsal root ganglia,
sympathetic ganglionic chains, the
enteric nervous system
The enteric nervous system (ENS) or intrinsic nervous system is one of the main divisions of the autonomic nervous system (ANS) and consists of a mesh-like system of neurons that governs the function of the gastrointestinal tract. It is capable of ...
and
melanocytes
Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea),
the inner ear,
vaginal epithelium, meninges,
bones,
and hear ...
. ZEB2 is also found in tissues that are not derived from the neural crest, including the wall of the digestive tract, kidneys, and skeletal muscles.
Clinical significance
Mutations in the ZEB2 gene are associated with the
Mowat–Wilson syndrome. This disease exhibits
mutation
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, m ...
s and even complete deletions of the ZEB2 gene. Mutations of the gene can cause the gene to produce nonfunctional ZEB2 proteins or inactivate the function gene as a whole. These deficits of ZEB2 protein interfere with the development of many organs. Many of the symptoms can be explained by the irregular development of the structures from the neural crest.
Hirschsprung's disease
Hirschsprung's disease (HD or HSCR) is a birth defect in which nerves are missing from parts of the intestine. The most prominent symptom is constipation. Other symptoms may include vomiting, abdominal pain, diarrhea and slow growth. Symptoms u ...
also has many symptoms that can be explained by lack of ZEB2 during development of the digestive tract nerves. This disease causes severe constipation and enlargement of the colon.
References
Further reading
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External links
GeneReviews/NIH/NCBI/UW entry on Mowat-Wilson syndrome*
{{DEFAULTSORT:Zeb2
Transcription factors