Homeobox protein DLX-5 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 distal-less homeobox 5 gene, or ''DLX5''

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 ...

. DLX5 is a member of

DLX gene family Genes in the ''DLX'' family encode homeodomain transcription factors related to the ''Drosophila'' distal-less ''(Dll)'' gene. The family has been related to a number of developmental features such as jaws and limbs. The family seems to be well pre ...

Function

This gene encodes a member of a homeobox transcription factor gene family similar to the ''

Drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many speci ...

'' 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 Homeobox protein DLX-6 is a protein that in humans is encoded by the ''DLX6'' gene. This gene encodes a member of a homeobox transcription factor gene family similar to the Drosophila ''Drosophila'' () is a genus of flies, belonging to the ...

can be seen to work in conjunction and are both necessary for proper craniofacial, axial, and appendicular skeleton development. Mutation in this gene, which is located in a tail-to-tail configuration with another member of the family 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 differentiation by stimulating the up-regulation of a variety of promoters (

ALPL Alkaline phosphatase, tissue-nonspecific isozyme is an enzyme that in humans is encoded by the ''ALPL'' gene. Function There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/k ...

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 refe ...

promoter).

Clinical significance

Mutations in the ''DLX5'' gene have been shown to be involved in the hand and foot malformation syndrome. 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 locali ...

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

, bone, inner ear, and severe craniofacial defects are prevalent. Research utilizing Dlx5/6-nulls suggests that these genes have both unique and redundant functions.

Developmental Stage

DLX5 begins to express DLX5 protein in the facial and

branchial arch Branchial arches, or gill arches, are a series of bony "loops" present in fish, which support the gills. As gills are the primitive condition of vertebrates, all vertebrate embryos develop pharyngeal arches, though the eventual fate of these arc ...

mesenchyme,

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 Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with

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 Microsoft and 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, then vice- ...

References

External links