Hox Genes and Homeotic Transformations

Hox Genes

• Named after the homeobox, a specific protein fold that evolved to bind DNA.
• William Bateson (1894) first described homeotic transformations and coined the term HOMEOSIS.
• HOMEOSIS is the replacement of part of one segment of a segmented animal (like an insect) with a structure characteristic of a different segment. For example, a leg could be replaced by a wing.
• Homeotic genes were first identified.

A gene complex controlling segmentation in Drosophila

• The bithorax gene complex in Drosophila has at least 8 genes that control thoracic and abdominal development.
• The level of repression of at least four of these genes is controlled by cis-regulatory elements.
• A separate locus, called Polycomb, seems responsible for a repressor protein of the complex.
• The state of repression of the genes is controlled via an antero-posterior gradient in the embryo, and a proximo-distal gradient on the chromosome.

Homeotic Selector Genes

• Shown diagrammatically as a fly's body plan and the genes responsible for development.
• The diagram indicates the Antennapedia complex and the bithorax complex, with corresponding genes (e.g., Antp, Ubx, abdA, AbdB) mapped along the head-to-tail axis.
• The diagram shows the correlation between the genes' positions on the chromosome and their expression patterns along the body.

Spatial Colinearity

• The ordering of Hox genes along the chromosome corresponds to their expression patterns along the body axis (head to tail).

Other Genes Involved

• Engrailed: Not a Hox gene but is regulated by Hox genes. Plays a role in segment polarity (defines anterior versus posterior of a segment),
• Antennapedia: A Hox gene.
• Ultrabithorax: A Hox gene.
• Distal-less: Not a Hox gene but regulated by Hox genes. Important for limb development, especially in humans with related genes DLX.

Additional Information on Hox Genes

• Hox genes are transcribed posterior to anterior in relation to the embryo (body).
• Hox genes encode members of the homeodomain protein family.
• These Hox gene proteins bind to DNA, allowing them to control genes, which in turn trigger the development of specific regions of the body.

Functional Redundancy

• Multiple Hox genes can perform the same function.
• This redundancy allows for flexibility and robustness in development.

Transition to Active Chromatin States

• The transition to active chromatin states determines which Hox genes are expressed.
• This process occurs in the developing embryo as somites are constructed.
• Somites are blocks of body tissue; the first somite forms first, somites 2 and 3 are under construction and others will be the next somites.
• FGF is a protein associated with this process influencing formation of the neural tube in embryos.

Hox Genes and Vertebrae

• Somites give rise to vertebrae.
• The shape of the vertebrae is determined by the Hox genes expressed within the somite.
• Hox gene expression patterns differ between chicken and mouse, leading to different vertebral patterns.

Regulatory Mechanisms

• Activation and repression by a colinear Hox code control specific Hox gene expression.
• Shown are images of chicken and mouse embryos illustrating Hox gene expression patterns.

Hox Genes and Limb Development

• Hox genes regulate proximal-distal patterning in limb development.
• Hox genes are essential for specific limb development (forelimb and hindlimb) and dictate which genes (and therefore what tissues) are developing.

Hox Gene Misexpression

• Incorrect expression of Hox genes can result in developmental abnormalities.
• This is shown by images of mouse embryos and human limbs with mis-expression of Hox genes causing anomalies.

Extreme Selection in Humans

• There is a high level of selection against homeotic transformations of the cervical vertebrae in humans.
• In humans, there are almost always exactly 7 cervical vertebrae.
• Fetuses with additional cervical ribs have a very high rate of death before birth or developmental abnormalities, indicating that natural selection strongly favors keeping the cervical vertebrae count stable and unchanging at 7 rather than more than 7 (or less than 7).

Explore the fascinating world of Hox genes, which play a crucial role in the segmentation and development of organisms, particularly in Drosophila. This quiz covers the concepts of homeosis, gene complexes, and regulatory mechanisms that govern developmental processes. Test your understanding of these fundamental genetic principles!