Teashirt zinc finger homeobox 1 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 TSHZ1
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 ...
.
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Function
This gene encodes a colon cancer
antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune respons ...
that was defined by serological analysis of recombinant cDNA expression libraries. The encoded protein is a member of the teashirt C2H2-type
zinc-finger
A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struc ...
protein family and may be involved in transcriptional regulation of developmental processes. Mutations in this gene may be associated with congenital
aural atresia syndrome.
In Animal Models
In addition to humans,
orthologous
Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a s ...
Tshz-family genes are known to exist in several other organisms, including invertebrates like insects. Research using
model organisms
A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the working ...
can be majorly beneficial in exploring the potential functionality of genes that are present in humans without requiring human testing. Additionally, by looking at gene number and function changes between organisms with differing levels of relatedness, it is possible to gain a better understanding of the gene’s
phylogeny
A phylogenetic tree (also phylogeny or evolutionary tree Felsenstein J. (2004). ''Inferring Phylogenies'' Sinauer Associates: Sunderland, MA.) is a branching diagram or a tree showing the evolutionary relationships among various biological spe ...
, or evolutionary history. Findings related to Tshz1 orthologs in model organisms varies in scale and density of research from organism to organism.
In Mice
Mice are commonly used to study Tshz1 functionality due to their closer relatedness to humans as mammals compared to other common model organisms. However, Tshz1 genes in non-model mammalian organisms have been characterized, or explored in detail, to a limited extent. The Tshz1 ortholog in the ''Mus musculus'' mouse model has been implicated in motor neuron development and craniofacial morphogenesis. Experiments involving whole gene knockout of Tshz1 during development resulted in universal lethality of M. musculus pups shortly after birth, presumably due to soft palate defects and skeletal deformities linked with Tshz1 inactivation.
Mutant mice in knockout and loss of function experiments have been observed to be unable to suckle and feed, with their intestines filling up with air shortly after birth and their stomach appearing distended compared to
wild type
The wild type (WT) is the phenotype of the typical form of a species as it occurs in nature. Originally, the wild type was conceptualized as a product of the standard "normal" allele at a locus, in contrast to that produced by a non-standard, "m ...
individuals.
Investigations into Tshz1 impact on motor neuron development have been limited in scale, however Tshz1 mutant mice have been observed to have difficulties regulating breathing, due to decreased survival of
Hypoglossal nerve
The hypoglossal nerve, also known as the twelfth cranial nerve, cranial nerve XII, or simply CN XII, is a cranial nerve that innervates all the extrinsic and intrinsic muscles of the tongue except for the palatoglossus, which is innervated by ...
and
phrenic
The phrenic nerve is a mixed motor/sensory nerve which originates from the C3-C5 spinal nerves in the neck. The nerve is important for breathing because it provides exclusive motor control of the diaphragm, the primary muscle of respiration. ...
motor neurons during development.
In Zebrafish
Tshz1 orthologs in ''Danio rerio'' have largely yet to be characterized, however experiments using
in-situ hybridization to mark gene expression have shown that Tshz1a is most highly expressed in the spinal cord, fore-to-hindbrain, and eye during early development.
Consequently, it is suspected that Tshz1a may play a role in neuron development in the brain and visual system, including the retina.
Three other Tshz family genes are known to exist in Zebrafish: Tshz2, Tshz3a, and Tshz3b. A fifth gene, Tshz1b, is predicted to exist. Multiple versions of the same gene commonly exist in the Zebrafish genome, referred to as ‘a’ and ‘b’, due to an evolutionary event known as
WGD (Whole Genome Duplication) in the ancestral lineage of
Teleost
Teleostei (; Greek ''teleios'' "complete" + ''osteon'' "bone"), members of which are known as teleosts ), is, by far, the largest infraclass in the class Actinopterygii, the ray-finned fishes, containing 96% of all extant species of fish. Tele ...
fish, which Zebrafish belong to. The potential existence of Tshz1b is therefore contingent on whether or not the Tshz1 ortholog in the Zebrafish ancestor existed prior to the WGD event/events, and if so, whether or not Tshz1b was lost subsequently over time due to chromosome rearrangement.
In Fruit Flies
''Drosophila melanogaster'' is known to possess one Tshz family gene, commonly referred to as Tsh or T Shirt, and is known to be orthologous to the Tshz gene family in humans and other vertebrates.
Tsh has been found to be involved in DNA-binding activity and several aspects of development, including formation of head structures and wing hinge development. Other important processes Tsh is involved in include segmental identity, dorsal/ventral patterning, and development of the compound eye.
Additionally, Tsh has been used as a test gene for creating more streamlined methods for determining the position of
enhancer elements due to its large ratio of
non-coding RNA
A non-coding RNA (ncRNA) is a functional RNA molecule that is not Translation (genetics), translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally im ...
s. While distantly related to humans, the presence of a Tshz-family gene in D. melanogaster suggests that this gene family originates early in the evolutionary lineage of modern-day organisms, before the divergence of vertebrate and invertebrate eukaryotes. Currently, no non-eukaryotic organisms are known to possess a Tshz-orthologous gene, but several other invertebrates, such as ''Bactrocera latifrons'' and ''Ceratitis capitata''
have known Tsh orthologs.
References
Further reading
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Genes on human chromosome 18
{{gene-18-stub