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 ...

protein DLX-5 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 in humans is encoded by the distal-less homeobox 5 gene, or ''DLX5''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. DLX5 is a member of the DLX gene family.

Function

This gene encodes a member of 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 ...

transcription factor gene family similar to the ''

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 ...

'' distal-less (Dll) gene. The encoded protein may play a role in bone development and fracture healing. Current research holds that the homeobox gene family is important in appendage development. DLX5 and DLX6 can be seen to work in conjunction and are both necessary for proper craniofacial, axial, and appendicular skeleton development. Mutations in this gene, which is located in a tail-to-tail configuration with ''DLX6'' on the long arm of chromosome 7, may be associated with split-hand/split-foot malformation. DLX5 also acts as the early BMP-responsive transcriptional activator needed for

osteoblast Osteoblasts (from the Greek combining forms for " bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts fu ...

differentiation by stimulating the up-regulation of a variety of promoters ( ALPL promoter, SP7 promoter,

MYC ''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' ( MYC), ''l-myc'' ( MYCL), and ''n-myc'' ( MYCN). ''c-myc'' (also sometimes r ...

promoter).

Clinical significance

Mutations in the ''DLX5'' gene have been shown to be involved in the split hand and foot malformation syndrome (SHFM). SHFM is a heterogenous limb defect in which the development of the central digital rays is hindered, leading to missing central digits and claw-like distal extremities. Other defects associated with DLX5 include sensorineural hearing loss, mental retardation,

ectodermal The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from the o ...

and craniofacial findings, and orofacial clefting. In mice, the targeted disruption of

DLX1 Homeobox protein DLX-1 is a protein that in humans is encoded by the ''DLX1'' gene. Function This gene encodes a member of a homeobox transcription factor gene family similar to the ''Drosophila'' distal-less gene. The encoded protein is loca ...

DLX2 Homeobox protein DLX-2 is a protein that in humans is encoded by the ''DLX2'' gene. Many vertebrate homeo box-containing genes have been identified on the basis of their sequence similarity with Drosophila developmental genes. Members of the Dlx ...

, DLX1/2, or DLX5 orthologs yields craniofacial, bone, and vestibular defects. If DLX5 is disrupted in conjunction with DLX6, bone, inner ear, and severe craniofacial defects are prevalent. Research utilizing Dlx5/6-nulls suggests that these genes have both unique and redundant functions.

Role in development

''DLX5'' begins to express DLX5 protein in the facial and

branchial arch Branchial arches or gill arches are a series of paired bony/ cartilaginous "loops" behind the throat ( pharyngeal cavity) of fish, which support the fish gills. As chordates, all vertebrate embryos develop pharyngeal arches, though the eve ...

mesenchyme Mesenchyme () is a type of loosely organized animal embryonic connective tissue of undifferentiated cells that give rise to most tissues, such as skin, blood, or bone. The interactions between mesenchyme and epithelium help to form nearly ever ...

otic vesicle Otic vesicle, or auditory vesicle, consists of either of the two sac-like invaginations formed and subsequently closed off during embryonic development. It is part of the neural ectoderm, which will develop into the membranous labyrinth of the in ...

s, and frontonasal ectoderm at around day 8.5-9. By day 12.5, DLX5 protein begins to be expressed in the brain, bones, and all remaining skeletal structures. Expression in the brain and skeleton begins to decrease by day 17.

Interactions

DLX5 has been shown to interact with

, DLX6,

MSX1 Homeobox protein MSX-1, is a protein that in humans is encoded by the ''MSX1'' gene. MSX1 transcripts are not only found in thyrotrope-derived TSH cells, but also in the TtT97 thyrotropic tumor, which is a well differentiated hyperplastic tissue ...

and

MSX2 MSX is a standardized home computer architecture, announced by ASCII Corporation on June 16, 1983. It was initially conceived by Microsoft as a product for the Eastern sector, and jointly marketed by Kazuhiko Nishi, the director at ASCII Cor ...

References

External links