What are HOX genes doing in planaria?

Our most recent preprint aims to shed some light on this puzzle

Before diving in, a brief history of past efforts to understand HOX genes in planaria is warranted

https://www.biorxiv.org/content/10.1101/2021.01.24.427972v1

@ScienceStowers @HHMINEWS @biorxivpreprint
The ancestral role of HOX genes has puzzled biologists for decades, a problem that ultimately intersected with the centuries-old debate of how the segmented body plan emerged in animals

https://science.sciencemag.org/content/361/6409/1310/tab-pdf
 
https://science.sciencemag.org/node/715894.full
 
@ScienceMagazine @wormduty @Gibson_Lab
The ancestral role of HOX genes has puzzled biologists for decades, a problem that ultimately intersected with the centuries-old debate of how the segmented body plan emerged in animals https://science.sciencemag.org/content/361/6409/1310/tab-pdf  https://science.sciencemag.org/node/715894.full  @ScienceMagazine @wormduty @Gibson_Lab
The ancestral role of HOX genes has puzzled biologists for decades, a problem that ultimately intersected with the centuries-old debate of how the segmented body plan emerged in animals https://science.sciencemag.org/content/361/6409/1310/tab-pdf  https://science.sciencemag.org/node/715894.full  @ScienceMagazine @wormduty @Gibson_Lab
Planaria have derivatives of ecto-, endo- and mesoderm, but lack visible segmentations in their body plan.

Hence, there has been a great deal of interest by developmental and evolutionary biologists in understanding HOX gene function in planaria.

https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.125.5322&rep=rep1&type=pdf
Planaria have derivatives of ecto-, endo- and mesoderm, but lack visible segmentations in their body plan.Hence, there has been a great deal of interest by developmental and evolutionary biologists in understanding HOX gene function in planaria. https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.125.5322&rep=rep1&type=pdf
Planaria have derivatives of ecto-, endo- and mesoderm, but lack visible segmentations in their body plan.Hence, there has been a great deal of interest by developmental and evolutionary biologists in understanding HOX gene function in planaria. https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.125.5322&rep=rep1&type=pdf
Planaria have derivatives of ecto-, endo- and mesoderm, but lack visible segmentations in their body plan.Hence, there has been a great deal of interest by developmental and evolutionary biologists in understanding HOX gene function in planaria. https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.125.5322&rep=rep1&type=pdf
HOX genes in planaria began to be cloned in the 1990’s

https://www.pnas.org/content/92/16/7227

@PNASNews
HOX genes in planaria began to be cloned in the 1990’s https://www.pnas.org/content/92/16/7227 @PNASNews
HOX genes in planaria began to be cloned in the 1990’s https://www.pnas.org/content/92/16/7227 @PNASNews
Intense efforts to define their spatial expression patterns followed soon after

https://dev.biologists.org/content/develop/124/1/141.full.pdf

https://www.sciencedirect.com/science/article/pii/S0012160699992758

@Dev_journal @Dev_Bio_Journal
Intense efforts to define their spatial expression patterns followed soon after https://dev.biologists.org/content/develop/124/1/141.full.pdf https://www.sciencedirect.com/science/article/pii/S0012160699992758 @Dev_journal @Dev_Bio_Journal
Intense efforts to define their spatial expression patterns followed soon after https://dev.biologists.org/content/develop/124/1/141.full.pdf https://www.sciencedirect.com/science/article/pii/S0012160699992758 @Dev_journal @Dev_Bio_Journal
One effort in Dugesia tigrina reported that HOX genes did not distinguish between anterior and posterior ends

The authors concluded their observation “...questions the conserved function attributed to the Hox cluster genes in anteroposterior positional information”

@Dev_journal
Two years later (1999), another study in Dugesia japonica contradicted the findings in D. tigrina.

It reported that the HOX genes of D. japonica were expressed gradually along the anteroposterior axis.

@Dev_Bio_Journal
The authors also reported that expression of the D. Japonica HOX genes were “...expressed along the A-P axis...” and concluded that they “may be the involved in A-P patterning during regeneration, as in other higher organisms”

@Dev_Bio_Journal
The authors also reported that expression of the D. Japonica HOX genes were “...expressed along the A-P axis...” and concluded that they “may be the involved in A-P patterning during regeneration, as in other higher organisms” @Dev_Bio_Journal
The authors also reported that expression of the D. Japonica HOX genes were “...expressed along the A-P axis...” and concluded that they “may be the involved in A-P patterning during regeneration, as in other higher organisms” @Dev_Bio_Journal
RNA mediated genetic interference was introduced in planaria the same year (1999)

https://www.pnas.org/content/pnas/96/9/5049.full.pdf
RNA mediated genetic interference was introduced in planaria the same year (1999) https://www.pnas.org/content/pnas/96/9/5049.full.pdf
RNA mediated genetic interference was introduced in planaria the same year (1999) https://www.pnas.org/content/pnas/96/9/5049.full.pdf
Many investigators used RNAi to target the HOX genes.

Unfortunately, no discernible defects were reported...

The question of what the expression patterns and functions of HOX genes may be in planarians remained unresolved.
When the first draft annotation of the genome of the diploid planaria Schmidtea mediterranea was published and made publicly available, it became clear that this flatworm had at least 13 HOX genes

https://doi.org/10.1093/nar/gkm684

@NAR_Open
By 2016, 10 HOX genes had been cloned across 6 species of planarians

https://www.sciencedirect.com/science/article/abs/pii/S1383576907001274?via%3Dihub

https://onlinelibrary.wiley.com/doi/full/10.1046/j.1440-169X.2001.00564.x

https://dev.biologists.org/content/develop/124/1/141.full.pdf

https://www.sciencedirect.com/science/article/pii/S0012160699992758

https://www.pnas.org/content/92/16/7227

https://link.springer.com/article/10.1007/s10528-008-9210-6
In 2016, Bret Pearson @SheckyFeinblatt and his trainees comprehensively defined the phylogenetic relationship of planaria HOX genes to other species

https://evodevojournal.biomedcentral.com/articles/10.1186/s13227-016-0044-8

@BioMedCentral
They also established definitive expression patterns of HOX genes in S. mediterranea

Unfortunately, as it was the case for other species, the authors wrote that “... no phenotype has been functionally ascribed to planarian HOX genes...”

https://evodevojournal.biomedcentral.com/articles/10.1186/s13227-016-0044-8

@BioMedCentral
They also established definitive expression patterns of HOX genes in S. mediterraneaUnfortunately, as it was the case for other species, the authors wrote that “... no phenotype has been functionally ascribed to planarian HOX genes...” https://evodevojournal.biomedcentral.com/articles/10.1186/s13227-016-0044-8 @BioMedCentral
They also established definitive expression patterns of HOX genes in S. mediterraneaUnfortunately, as it was the case for other species, the authors wrote that “... no phenotype has been functionally ascribed to planarian HOX genes...” https://evodevojournal.biomedcentral.com/articles/10.1186/s13227-016-0044-8 @BioMedCentral
So, what are HOX genes doing in planaria?
In 2019, we discovered that planaria had anatomical segments at regularly spaced intervals along the anterior-posterior axis that are revealed by exerting pressure on their bodies

https://www.nature.com/articles/s41586-019-1478-7#citeas

@cparnoldphd @BlairBenhamPyle
@ScienceStowers @HHMINEWS @nature
This altogether new finding led us to study the segments in greater detail

We observed that the number of segments scales proportionally with animal growth size and are added in a defined order

https://www.nature.com/articles/s41586-019-1478-7#citeas

@nature
This altogether new finding led us to study the segments in greater detailWe observed that the number of segments scales proportionally with animal growth size and are added in a defined order https://www.nature.com/articles/s41586-019-1478-7#citeas @nature
This altogether new finding led us to study the segments in greater detailWe observed that the number of segments scales proportionally with animal growth size and are added in a defined order https://www.nature.com/articles/s41586-019-1478-7#citeas @nature
We also found that the signaling pathways known to regulate anterior-posterior axis in planarians neither affected the number nor order of appearance of the compression planes in planaria@during either growth or regeneration.

https://www.nature.com/articles/s41586-019-1478-7#citeas

@nature
Given these new data, i.e., segments and an orderly appearance during growth along the anterior posterior axis, we hypothesized a possible role for HOX genes in this process.

We tested their functions using RNAi

https://www.biorxiv.org/content/10.1101/2021.01.24.427972v1.article-metrics

@biorxivpreprint
We found that RNAi of post2b eliminated the deposition of segments and that Hox 3 increased their number along the anterior-posterior axis

https://www.biorxiv.org/content/10.1101/2021.01.24.427972v1.article-metrics

@biorxivpreprint
We also found that HOX genes modulate behavior associated with asexual reproduction, likely a new role for these genes.

RNAi of post2b abrogated fission behavior and RNAi of hox3 increased it
Our findings indicate that HOX genes play conserved roles in the regulation of axial patterning in adult planaria.
But we also postulate that the regulation of asexual reproduction and/or the specification of neural circuitry utilized in this process may represent an ancestral function
for HOX genes.
Want to learn more?

Please read our pre-print

https://www.biorxiv.org/content/10.1101/2021.01.24.427972v1

@biorxivpreprint
Hox genes regulate asexual reproductive behavior and tissue segmentation in adult animals

Hox genes are highly conserved transcription factors renowned for their roles in the segmental patterning of the embryonic anterior-posterior (A/P) axis[1][1]. Emerging evidence for Hox gene expres...

https://www.biorxiv.org/content/10.1101/2021.01.24.427972v1
And for a great thread on the findings reported in our preprint, visit @cparnold for a great thread on these data!
You can follow @Planaria1.
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