Misexpression

Misexpression refers to the expression of a gene in a context in which it is not normally expressed, such as in the wrong tissue, at the wrong developmental stage, or at abnormal levels. It contrasts with normal, regulated expression patterns that align with tissue, time, and dosage requirements.

Causes include mutations in cis-regulatory elements (enhancers, silencers, promoters) that alter when and where a gene is turned on; copy number changes leading to overexpression; epigenetic changes; trans-acting factors; and experimental manipulation such as misexpression studies using ectopic promoters.

Categories of misexpression include spatial misexpression (ectopic expression in non-native tissue), temporal misexpression (precocious or delayed expression), and dosage misexpression (overexpression or underexpression).

Impacts can be significant, including disruption of development and physiology. Ectopic expression of developmental regulators can cause morphological abnormalities, and misexpression of oncogenes or tumor suppressors can contribute to cancer. In model organisms, ectopic misexpression of HOX genes can lead to homeotic transformations, while misexpression of signaling molecules like Sonic hedgehog in limb buds can produce limb patterning defects such as polydactyly.

Applications of studying misexpression include probing gene function and regulatory networks in research, using misexpression constructs to uncover tissue- and time-specific roles of genes. Therapies and genome-editing approaches also aim to address pathogenic misexpression by restoring appropriate regulatory control or expression levels.

Detection and study rely on methods such as gene expression profiling, in situ hybridization, immunohistochemistry, reporter assays, and inducible promoters to control timing and location of expression.