Ladybird homeobox 2 (LBX2) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that is encoded by the ''LBX2'' gene, located on the second chromosome in

humans Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

, and on the sixth chromosome in

mice A mouse (: mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

. LBX2 belongs to the

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 family, which plays important roles in embryonic development and tissue differentiation. The protein encoded by LBX2 functions as 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 (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

and is expressed in various tissues, including the heart, skeletal muscle, and nervous system. LBX2 is involved in the regulation of cardiac development, particularly in the formation of the atrial septum. Mutations or dysregulation of LBX2 have been associated with an increased risk of congenital heart defects, specifically

atrial septal defect Atrial septal defect (ASD) is a congenital heart defect in which blood flows between the atrium (heart), atria (upper chambers) of the heart. Some flow is a normal condition both pre-birth and immediately post-birth via the Foramen ovale (heart) ...

s. LBX2 plays a significant role in the development of various

organs In a multicellular organism, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to a ...

, such as the

heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...

, and has been implicated in the growth of certain

cancers Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

Gene structure

The LBX2 gene shares similarities with its rodent counterpart, also named LBX2, in genomic structure. Both human and rodent LBX2 genes are composed of two

exons An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence i ...

separated by an

intron An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of the cistron .e., gen ...

. The upstream region of the mouse LBX2, which shares a high degree of similarity to its human counterpart, has also been observed to be a

regulatory sequence A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and vir ...

that influences the expression of reporter genes. This regulatory influence is tissue-specific, highlighting the complexity of gene expression in different biological contexts.

Expression and function

LBX2 is a member of the ladybird family of

homeobox genes A homeobox is a 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 the full-grown organism ...

, which are crucial in developmental processes. In rodent studies, LBX2 has been found to be expressed in various developing systems, notably the

urogenital system The genitourinary system, or urogenital system, are the sex organs of the reproductive system and the organ (biology), organs of the urinary system. These are grouped together because of their proximity to each other, Development of the urinary a ...

eye An eye is a sensory organ that allows an organism to perceive visual information. It detects light and converts it into electro-chemical impulses in neurons (neurones). It is part of an organism's visual system. In higher organisms, the ey ...

, and

brain The brain is an organ (biology), organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head (cephalization), usually near organs for ...

. CRISPR/Cas9 technology has been used to create zebrafish models lacking LBX2. Observations of these modified zebrafish revealed several notable differences compared to normal specimens, including: * Enlarged heart chambers (the atrium and ventricle) * Disorganized distribution of

cardiac myocytes Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of ...

* Delayed migration of cardiac neural crest cells These findings suggest that LBX2 plays a significant role in the development of the

Clinical significance

Alström syndrome

While polymorphisms in the LBX2 gene have been identified, studies indicate that mutations in the coding region of LBX2 do not account for

Alström syndrome Alström syndrome (AS), also called Alström–Hallgren syndrome, is a very rare autosomal recessive genetic disorder characterised by childhood obesity and multiple organ dysfunction. Symptoms include early-onset type 2 diabetes, cone-rod dyst ...

, a genetic disorder characterized by ocular and urogenital abnormalities.

Atrial septal defect

A study aimed at identifying causal genes for ostium secundum atrial septal defect (ASD) discovered that a rare

missense mutation In genetics, a missense mutation is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid. It is a type of nonsynonymous substitution. Missense mutations change amino acids, which in turn alt ...

in LBX2 was associated with this condition.

Ovarian cancer

Laboratory studies have indicated that LBX2 promotes rapid

cell proliferation Cell proliferation is the process by which ''a cell grows and divides to produce two daughter cells''. Cell proliferation leads to an exponential increase in cell number and is therefore a rapid mechanism of tissue growth. Cell proliferation ...

in ovarian cancers and is a key gene involved in ovarian cancer formation. It has been identified as a potential target for therapeutic interventions.

Lung cancer

Lung adenocarcinoma (LUAD) is the most common type of lung cancer. Studies have shown that reducing LBX2 expression inhibits LUAD growth, whereas its overexpression promotes tumor growth and invasiveness. In most LUAD cases, LBX2 is expressed at elevated levels, correlating with poor clinical outcomes.

Conclusion

LBX2 is a crucial gene involved in development and

disease A disease is a particular abnormal condition that adversely affects the structure or function (biology), function of all or part of an organism and is not immediately due to any external injury. Diseases are often known to be medical condi ...

processes. Its role in the development of organs, particularly in the

cardiac The heart is a muscular organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrients to the tissu ...

and reproductive systems, alongside its implications in cancer biology, emphasise its importance to the healthy development of

rodents Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia ( ), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are n ...

and

zebrafish The zebrafish (''Danio rerio'') is a species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (an ...

References

{{Transcription factors and intracellular receptors, g3 Genes on human chromosome 2 Oncogenes