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Overview
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Background
Aristaless-related genes are a group of paired-related homeobox genes which play a role in regulating vertebrate embryogenesis. The homeodomain transciption factor aristaless-like 3 (ALX3) is expressed in mouse embryos from 8 days of gestation, predominantly in neural crest-derived mesenchyme and in lateral plate mesoderm. Expression analysis of human and mouse tissue reveals predominant ALX3 expression in brain tissue. The Alx3 gene maps to chromosome 1p23-p13 and encodes a 343 amino acid protein. Preferential methylation of Alx3 occurs in advanced-stage neuroblastoma and may repress ALX3 expression. Treatment with the methylation inhibitor 5-aza-2’-deoxycytidine restores ALX3 expression. Alx3 (-) mice lack a phenotype distinct from wild-type mice, however Alx3/Alx4 double mutants demonstrate severe craniofacial abnormalities not present in Alx4 single mutants. Specifically, Alx3/Alx4 double mutant newborn mice have cleft nasal regions in addition to malformation of other neural crest-derived skull structures.
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