Orthodenticle (otd) is a

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

gene found in Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...
that regulates the development of anterior patterning, with particular involvement in the central nervous system function and eye development. It is located on the

X chromosome The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...

. The gene is an

ortholog 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 speci ...

of the human OTX1/ OTX2 gene.

Function

During embryonic Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...
development, otd is required for the head and ventral midline to develop correctly. In the larval stage, otd is expressed in specific sac-like

epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

structures known as imaginal discs that later give rise to external structures of the head and

thorax The thorax (: thoraces or thoraxes) or chest is a part of the anatomy of mammals and other tetrapod animals located between the neck and the abdomen. In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main di ...

. Particularly, otd is required for the development of the dorsal region of the adult ''Drosophila'' head, that forms from the fusion of two eye-antennal discs. Distribution of the otd protein occurs along a concentration of the

imaginal disc An imaginal disc is one of the parts of a holometabolous insect larva that will become a portion of the outside of the adult insect during the pupal transformation to the imago. Contained within the body of the larva, there are pairs of discs t ...

primordia A primordium (; : primordia; synonym: anlage), in embryology, is an organ or tissue in its earliest recognizable stage of development. Cells of the primordium are called primordial cells. A primordium is the simplest set of cells capable of tr ...

for these head structures such that different levels of otd expression are required for differential mediolateral subdomains to be established. In ''Drosophila'', the function of otd as an essential factor in anterior pattern formation has been replaced by

Bicoid Homeotic protein bicoid is encoded by the ''bcd'' maternal effect gene in ''Drosophilia''. Homeotic protein bicoid concentration gradient patterns the anterior-posterior (A-P) axis during ''Drosophila'' embryogenesis. Bicoid was the first prot ...

, another

homeodomain A homeobox is a Nucleic acid sequence, DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. Mutations in a homeobox may change large-scale anatomical features of ...

protein which is involved in anterior patterning such that ''bcd'' mRNA is sequestered at the anterior pole of the mature

oocyte An oocyte (, oöcyte, or ovocyte) is a female gametocyte or germ cell involved in reproduction. In other words, it is an immature ovum, or egg cell. An oocyte is produced in a female fetus in the ovary during female gametogenesis. The female ger ...

. In the absence of ''bcd'', all anterior structures of the embryo including the

cephalic A head is the part of an organism which usually includes the ears, brain, forehead, cheeks, chin, eyes, nose, and mouth, each of which aid in various sensory functions such as sight, hearing, smell, and taste. Some very simple animals may no ...

and

thoracic The thorax (: thoraces or thoraxes) or chest is a part of the anatomy of mammals and other tetrapod animals located between the neck and the abdomen. In insects, crustaceans, and the extinct trilobites, the thorax is one of the three main ...

segments fail to develop, and duplications of posterior structures are observed instead. Additionally, otd is involved in development of all eight photoreceptors of adult ''Drosophila'' in each of their ~700 individual eye units, known as

ommatidia The compound eyes of arthropods like insects, crustaceans and millipedes are composed of units called ommatidia (: ommatidium). An ommatidium contains a cluster of photoreceptor cells surrounded by support cells and pigment cells. The outer part ...

and their proximal-distal distribution in the eye. The two types of photoreceptors, outer (OPRs) and inner (IPRs), are distinguished through their function and anatomy such that OPRs have six

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s that respond to dim light conditions and are important for motion detection, while IPRs have two neurons that differentiate colour. OPRs possess light-gathering apical surfaces called rhabdomeres, and otd is required for rhabdomere morphogenesis. Rapid expression of otd in all OPRs and IPRs is found following neuronal cell specification in the late larval stage and persists through photoreceptor differentiation. In later development of pupation through to adulthood, otd activates light detecting

rhodopsin Rhodopsin, also known as visual purple, is a protein encoded by the ''RHO'' gene and a G-protein-coupled receptor (GPCR). It is a light-sensitive receptor protein that triggers visual phototransduction in rod cells. Rhodopsin mediates dim ...

proteins Rh3 and Rh5 in IPRs while repressing Rh6 in OPRs.

Regulation

Embryo

In the anterior cap region of the

syncytial A syncytium (; : syncytia; from Greek: σύν ''syn'' "together" and κύτος ''kytos'' "box, i.e. cell") or symplasm is a multinucleate cell that can result from multiple cell fusions of uninuclear cells (i.e., cells with a single nucleus), in ...

blastoderm A blastoderm (germinal disc, blastodisc) is a single layer of embryonic epithelial tissue that makes up the blastula. It encloses the fluid-filled blastocoel. Gastrulation follows blastoderm formation, where the tips of the blastoderm begins the for ...

, which has non-segregated nuclei along the periphery of the blastoderm,

bicoid Homeotic protein bicoid is encoded by the ''bcd'' maternal effect gene in ''Drosophilia''. Homeotic protein bicoid concentration gradient patterns the anterior-posterior (A-P) axis during ''Drosophila'' embryogenesis. Bicoid was the first prot ...

in low concentrations is sufficient to activate otd expression through an enhancer located upstream of the otd gene. Later, in the cellular blastoderm, which has all nuclei along the periphery separated in individual cells with their own

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

, otd expression is limited to a dorsal and anterior band due to repression of

by torso, hunchback, and dorsal. Torso and hunchback expression represses otd expression in the anterior most region of the

while dorsal expression represses expression in the ventral region. Groucho-independent repression of otd by runt, a

pair-rule gene A pair-rule gene is a type of gene involved in the development of the segmented embryos of insects. Pair-rule genes are expressed as a result of differing concentrations of gap gene proteins, which encode transcription factors controlling pair-r ...

, has also been observed in the anterior and posterior regions of the

and cellular

Ocelliless

Ocelliless (oc) is a general

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, ...

in the otd gene locus in Drosophila ''Drosophila'' (), from Ancient Greek δρόσος (''drósos''), meaning "dew", and φίλος (''phílos''), meaning "loving", is a genus of fly, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or p ...
, which results in a loss of

ocelli A simple eye or ocellus (sometimes called a pigment pit) is a form of eye or an optical arrangement which has a single lens without the sort of elaborate retina that occurs in most vertebrates. These eyes are called "simple" to distinguish the ...

: the three photoreceptor organs located on the anterior region of Drosophila heads Two alleles ''oc¹'' and ''oc^γa1'', are caused by lesions downstream of the last exon in ''otd'' which showed enhancer activity. Another characteristic of the oc phenotype is the abnormal or deleted bristles in the ocellus region, which relates back to the

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, " ...

otd gene’s role in mediating anterior patterning. The same ''oc'' phenotype is found in loss-of-function ''epidermal growth factor receptor (EGFR)'' alleles and RNAi knockdown ''pointed (pnt)'' mutants The effect of ''oc'' on

can be complemented by ''otd^uvi'', another hypomorphic

allele An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule. Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...

of the ''otd'' gene. ''otd^uvi''/oc

heterozygotes Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

shows no ocellar phenotype or photoreceptor (R cell) phenotype, a phenotype that is related with ''otd^uvi''

. The Ocelliless mutant phenotype is not limited to loss of ocelli only. It has a role in disrupting

oogenesis Oogenesis () or ovogenesis is the differentiation of the ovum (egg cell) into a cell competent to further develop when fertilized. It is developed from the primary oocyte by maturation. Oogenesis is initiated before birth during embryonic devel ...

, where the inner and outer layer of the

chorion The chorion is the outermost fetal membrane around the embryo in mammals, birds and reptiles (amniotes). It is also present around the embryo of other animals, like insects and molluscs. Structure In humans and other therian mammals, the cho ...

in oc mutant eggs separate from one another leaving space for debris that is not seen in

''otd'', and disrupting reproductive capabilities, where female flies

homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

for the ''oc'' mutation are

sterile Sterile or sterility may refer to: *Asepsis, a state of being free from biological contaminants * Sterile (archaeology), a sediment deposit which contains no evidence of human activity *Sterilization (microbiology), any process that eliminates or ...

References

{{reflist Drosophila melanogaster genes