HOX gene mutations are associated with limb malformations in humans. Which general principle governs HOX gene expression in the vertebral column?

• A HOX genes are expressed uniformly along the entire vertebral axis
• B HOX genes are expressed only in cervical segments
• C More 5' HOX genes are expressed more cranially; more 3' genes are expressed more caudally
• D More 3' HOX genes are expressed more cranially; more 5' genes are expressed more caudally ✓

Explanation

HOX genes obey spatial colinearity: genes located at the 3' end of each HOX cluster are expressed at more cranial (anterior) levels, while genes at the 5' end are expressed at progressively more caudal levels. This pattern specifies vertebral identity along the craniocaudal axis — mutations in HOX genes can shift vertebral identity (homeotic transformations), such as a cervical vertebra acquiring thoracic characteristics. This 3'-to-cranial rule applies across all four HOXA-D clusters in humans.

Reference: BD Chaurasia's Human Anatomy, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.