BioTechniques On How Hox Genes Control the Way We Look

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A study involving CRISPR gene editing in Drosophila has demonstrated the role of Hox genes in the development of anatomical appearance.

Many scientists and researchers are familiar with the “McGinnis experiment” (1990), which saw the biologist William McGinnis uncover how Hox (high-level control) genes shape our physical features and make us look the way we do. He examined whether proteins encoded by the human or mouse Hox gene could function in flies and played a key role in the discovery of a defining DNA region. McGinnis coined this DNA region the “homeobox”, a sequence inside genes that directs anatomical development.

Three decades on, McGinnis’ mentee Ankush Auradkar has worked with Professor Ethan Bier (both at the University of California, San Diego) to lead a new study on Hox genes, which explores how these genes determine the identities of different body regions. In November 2021, Science Advances published the study, which has unveiled new clues into the fundamental development of anatomical appearance.

Here, the life sciences journal BioTechniques explains how Auradkar and Bier built on the original study, using CRISPR gene editing technology to examine the role of Hox genes in the development of anatomical facial features of Drosophila flies.

The Original “McGinnis Experiment

The original “McGinnis experiment” revealed how Hox genes can adjust physical anatomical development. The study provided the scaffolding for scientists to understand the role that Hox genes play in determining uniform appearances in any species. That said, some questions were left unanswered. For example, the study left scientists wondering whether Hox genes provide “positional codes” that act as a framework to regulate downstream expression patterns or whether they themselves instruct morphological changes. In the context of evolution, many scientists also questioned the importance of coding versus regulatory sequence changes.

The Follow-Up Study

In the new study, Auradkar and Bier hoped to answer these questions and understand the function of Hox genes. They leveraged a modern CRISPR gene editing technique to test whether they could replace all aspects of the Hox gene function in a common laboratory fruit fly, the Drosophila melanogaster (D. mel), with its counterpart from a rarer Hawaiian cousin, the Drosophila mimica (D. mim), which have very different faces. After performing a whole-genome extraction, the research team sequenced the genome of both fruit flies. They carried out this sequencing using a combination of short (Illumina) reads and long (Sanger) reads.

The research team then applied a CRISPR gene editing technique to replace the “proboscipedia” (pb) locus (a Hox gene) from the D. mel genome with a copy of the pb gene from the D. mim. This gene informs the formation of the strikingly different mouthparts between the two species. While the D. mel’s mouthpart looks smooth, the D. mim’s mouthpart looks more angular.

Study Findings

As McGinnis had predicted, the D. mel’s smooth mouthparts triumphed over the angular mouthparts encoded by the D. mim pb sequence introduced to the genome. The study concluded that Hox genes lay the foundations for downstream genes that best benefit the organism, instead of directly instructing morphological changes.

Although the D. mel’s features triumphed overall, a shift in the control region led the research team to observe a different pattern of pb gene activation. The sensory organs (maxillary palps) on the face of the D. mel usually stick out. However, the study found the sensory organs to be parallel to the mouthparts, much like in the D. mim fruit fly. This finding suggests that pb sequences can evolve in closely linked species to alter morphology.

“These insights may lead to a better understanding of processes tied to congenital birth defects in humans,” Bier said. “With the advent of powerful new CRISPR-based genome editing systems for human therapy on the horizon, new strategies might be formulated to mitigate some of the effects of these often-debilitating conditions.”

The findings of the study have implications for evolutionary biology in Drosophila and may help explain developmental issues connected with human genetic processes.

Providing Scientists and Researchers the Latest Resources

The peer-reviewed, open-access journal BioTechniques publishes the latest information and insights into lab methodologies, technologies, and tools. Some of these methodologies include CRISPR gene editing, western blotting, next-generation sequencing, polymerase chain reaction (PCR), and chromatography. The past four decades have seen the life sciences journal provide scientists, research professionals, and students from all corners of the globe with invaluable resources, both in print and on BioTechniques’ multimedia website. The website supplements the journal with a wealth of webinars, videos, infographics, eBooks, podcasts, and a platform to engage in meaningful industry discussions.

BioTechniques is a Future Science Group journal. The progressive medical and scientific publisher distributes 34 journals, including Future Oncology and Regenerative Medicine, and hosts several online community websites. The Group also manages a variety of events, creative services, and publishing solutions.

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