The Hox code


Blogging on Peer-Reviewed Research

The Hox genes are a set of transcription factors that exhibit an unusual property: they provide a glimpse of one way that gene expression is translated into metazoan morphology. For the most part, the genome seems to be a welter of various genes scattered about almost randomly, with no order present in their arrangement on a chromosome — the order only becomes apparent in their expression through the process of development. The Hox genes, on the other hand, seem like an island of comprehensible structure. These are all genes that specify segment identity — whether a segment of the embryo should form part of the head, thorax, or abdomen, for instance — and they’re all clustered together in one (usually) tidy spot.

Within that cluster, we see further evidence of order. Look at just the Drosophila part of the diagram below: there are 8 Hox genes in a row, and their order within that row reflects the order of expression in the fly body. On the left or 3′ end of the DNA strand, lab (labial) is expressed in the head, while Abd-B (Abdominal-B) is expressed at the end of the abdomen.

i-3d10d2b119aa766df39871ead4a8a19c-hoxcode_hox.gif
Schematic of relationship between Drosophila and mouse Hox genes. Hox genes are shown as colored boxes in their order on the chromosome. Orthologous genes between Drosophila and mouse, and paralogous mouse genes are shown color-coded.

Knocking out individual Hox genes in the fly causes homeotic transformations — one body part develops into another. These genes are early actors in the cascade of interactions that enable the development of morphologically distinct regions in a segmented animal — the activation of a Hox gene from the 3′ end is one of the earliest triggers that leads the segment to develop into part of the head.

Now look at the mouse part of the diagram above. We vertebrates have Hox genes that are homologous to the fly Hox genes, and they’re also clustered in discrete locations with 3’→5′ order reflecting anterior→posterior order of expression. There are differences — the two most obvious that we have more Hox genes on the 5′ side (these correspond to expression in the tail—flies do not have anything homologous to the chordate tail), and vertebrates also have four banks of Hox genes, HoxA, HoxB, HoxC, and HoxD. This complicates matters. Vertebrates have these parallel, overlapping sets of Hox genes, which suggests that morphology could be a product of a combinatorial expression of the genes in the four Hox clusters: there could be a Hox code, where identity can be defined with more gradations by mixing up the bounds of expression of each of the genes.

In the fly, we have a relatively easy situation. Since each segment more or less expresses only one Hox gene, mutating or knocking out a single Hox gene will have an effect on a corresponding segment. In the chordate, though, each segment has at least two and in some cases four Hox genes that may be involved in its development. There is the possibility of redundancy here.

For instance, the HoxA3 gene is expressed in the anterior cervical vertebrae, in the neighborhood of the region where the first neck vertebra articulates with the skull. Deleting HoxA3 had no detectable effects on that joint, however; either its influence is too subtle to be measure, or it has effects on some other aspect of cervical specification, or it has a partner gene that takes over its job in its absence. Notice in the diagram above that HoxA3 has a paralog, or copy, called HoxD3 which is expressed in a very similar place. When HoxD3 is mutated all by itself, there are serious abnormalities: the first neck vertebra has a partial fusion with the base of the skull.

Knock out both HoxA3 and HoxD3, though, and we see evidence that HoxA3 is important after all: the first neck vertebra doesn’t form at all. In fact, it’s thought that the initial mesodermal tissue for the bone has been so thoroughly respecified that it instead fuses completely with the skull, becoming part of the base of the skull.

These results tell us that a combination of Hox genes are required for the proper development of the first cervical vertebra. They also complicate analyses. They say that if you try to knock out the Hox genes one at a time in the mouse, there will be cases where you will see no phenotype or only a partial phenotype, even when the gene does have an important role to play in that segment. What needs to be done is knock out all of the paralogous genes. That is, in order to see what the third Hox genes in the clusters do, we need to carry out a paralogous deletion that destroys the function of HoxA3, HoxB3, and HoxD3 (there is no HoxC3) to assess the phenotype.

This phenomenon is also one reason why we so rarely see homeotic mutations in vertebrates. In flies, you can mutate one gene and you get a haltere transformed into a wing or an antenna turned into a leg; in the mouse, you need to simultaneously zap 2 to 4 genes to get a similar complete transformation.

Now the technology has progressed to the point where we’re starting to see published descriptions of mice with complete paralogous sets knocked out. Look below!

i-96a0297fde5634dbc263a3c92f373a5f-hoxcode_paralogous_mutants.jpg
Changes in specific vertebral elements for the Hox5, Hox6, Hox9, Hox10, and Hox11 paralogous mutants. On the left side of the panel, a diagram of the axial skeleton is shown, with specific vertebral elements shown in the right panel marked (C, cervical; T, thoracic; L, lumbar, S, sacral). Wild-type, control elements from specific vertebral positions are denoted by letter and number. The analogous segment from the paralo- gous mutants are shown on the right and left, with colored boxes for each paralogous mutant group.

The cartoon on the left illustrates the skeletal morphology that was assessed. At the top are the cervical vertebrae, C1-C7, which have no ribs. Next are the ribbed thoracic vertebrae, T1-T13.T1-T7 also wrap around to connect to the sternum, which is part of the abaxial skeleton (the vertebrae are part of the primaxial skeleton). Then come the lumbar vertebrae, L1-L6, the sacral vertebrae S1-S4 (which articulate with the pelvis), and the many small tail vertebrae. Each has a discrete, recognizable morphology.

On the right, we see cross-sections of these vertebrae. The middle column is the normal control — that’s what the vertebrae are supposed to look like in a non-mutant mouse. On either side are the mutant forms for each of the paralogous mutants.

For example, look at T1 in the control. In addition to the oval profile of the vertebra, it’s supposed to have a stout pair of ribs. To the left, bordered in green, is the effect of a complete knockout of all the Hox5 genes — HoxA5, HoxB5, and HoxC5. The ribs have started to form, but are incomplete. This is a partial transformation towards a more cervical morphology. To the right, bordered in purple, is what happens to T1 when all of the Hox6 genes (HoxA6, HoxB6, and HoxC6) are taken out: it looks almost exactly like the control C7 vertebra. This is a complete homeotic transformation of T1 to C7.

Now here’s a dorsal view illustrating the effects of these paralogous knockouts.

i-6c99bf5726009d616ce1d97b31535e51-hoxcode_transformations.jpg
(click for larger image)

Schematic representation of regions of reported phenotypes in Hox paralogous mutants. Different vertebral elements are denoted by unique shapes, shown in the bottom panel . Aqua-shaded areas demonstrate the regions of anterior homeotic transformations of the somite-derived primaxial phenotypes. Purple-shaded areas show the lateral plate-derived, abaxial phenotypes for each group. The orange background highlights the regions of phenotypic overlap between adjacent paralogous mutants.

Each knockout affects a region. When all of the Hox9 genes are mutated, for example, we see an anterior shift in the midtrunk. The posterior thoracic segments now have ribs that meet the sternum — it’s as if T8-T13 are trying to be T1-T7. In addition, some of the lumbar vertebrae are confused and have acquired thoracic characters, sprouting ribs where there should be none. With these more complete knock-outs of paralogs, we see homeotic transformations all over the place!

Now we can pull the whole story together and map out the morphological domains over which each of these Hox paralogs hold sway.

i-11bef9539b06462fe0e792e0f79a8c67-hoxcode_overlap.jpg
Schematic of overlaps in and differences between the somite-derived primaxial phenotypes and the lateral plate-derived, abaxial phenotypes of Hox paralogous mutants. The regions for both primaxial and abaxial defects are shown as color-coded bars adjacent to the segments affected in paralogous mutants. Note the differences in AP position as well as the overlap differences in the primaxial versus the abaxial phenotypes.

Notice that not only do we have combinatorial arrangements within a bank of paralogs (those subtleties are not illustrated in the diagram above), but also combinations of sets of paralogs. The sacral segments, for instance, are defined by the expression of both Hox10 and Hox11 genes — one can imagine a kind of logical AND gate in the regulatory circuitry that switches on the downstream genes that signal the specific morphology required for joining to the pelvis only in the presence of both sets of Hox genes. Other experiments suggest that the ground state for a segment is to be thoracic-like and develop limbs; Hox10 and Hox11 may also have functions to suppress rib formation.

What the Hox code represents is a somewhat digital mechanism for regulating axial patterning. By mixing and matching combinations of the expression of a small number of Hox genes, the organism generates a greater range of morphological possibilities. The experiments described in this summary by Wellik are at a rather coarse level, revealing broad chunks of the Hox regulatory scheme, but future work should distill out the details and the specific and finer aspects of morphological regulation. Getting shape from genes is a difficult process to comprehend — the Hox system is one place where we’re getting closer.


Wellik DM (2007) Hox patterning of the vertebrate axial skeleton. Dev Dyn 236:2454-2463.

Comments

  1. lithopithecus says

    …uh, i wish i knew more latin, so i could say something cool like, “from redundncy, complexity”, but…

    …beautiful will have to suffice.

    oh yeah, First!

  2. sailor says

    Great post and understandable to we laypeople, thanks.
    I suppose it leads to the inevitable question:
    Could creationism be a result of mutation in the hox genes that control brain growth?

  3. Gelf says

    Knocking out individual Hox genes in the fly causes homeotic transformations

    I don’t even want to talk about how I misread this.

  4. noncarborundum says

    mutation in the hox genes

    Based on what I’ve seen of Hovind and his ilk, I’d say creationism is more likely to be associated with the Hoax genes.

  5. says

    Posts like this make me want to initiate a new Web Carnival (since we certainly don’t have enough of those) in, say Life Sciences, or maybe more general science, with slightly different rules: Submissi0s w0uld have t0 be 0riginal material and substantive.

    BTW, my 0h key is stuck, s0 I’m using the Zer0. What d0 I d0?????

  6. says

    Very nice indeed. Minor addition:

    “vertebrates also have four banks of Hox genes, HoxA, HoxB, HoxC, and HoxD”

    Roughly half of all vertebrates are teleost fishes, and they have 7 Hox clusters as a result of an additional round of genome duplication.

  7. says

    Yep. Unfortunately, we don’t have comparable experiments where a whole set of paralogous genes get knocked out in a fish — that will be interesting to see when it’s accomplished.

  8. Kausik Datta says

    Great, informative post. Thanks very much!

    A minor addition. Members of the human HOX gene family, homologous to Drosophila hox genes, are also hypothesized to play a role in the differentiation and lineage commitment during hematopoiesis. Human HOX genes clusters (HOXA though D) each contain 8-11 genes, designated sequentially within respective clusters. Early studies of human HOX gene expression and function, mainly done in leukemia cell lines, linked expression of a number of HOXA genes with erythroid lineage cells; HOXB genes, with myeloid differentiation; and the HOXC cluster, with the lymphoid lineages. HOXD expression was rare in hematopoietic cell lines. The role of the HOX genes in human hematopoietic differentiation appears to be extremely complex, as seen from studies of normal hematopoiesis.

    A good review is available in Immunological Review, 187(1):48, 2002.

  9. Joel says

    Great post.

    “Why does the order of genes mirror the order of body parts?”

    Great question. Spatial (and temporal) colinearity in the HOX clusters is still a mystery, but must surely have to do with the integration of regulatory mechanisms for this gene family. Seldom is a HOX cluster broken (though Meyers elides the disruption of colinearity in D. melanogaster, and the the cluster is broken in a different spot in D. virilis). The obvious hypothesis is that there’s an LCR that controls the expression of each HOX cluster, but apart from a LCR to control the subset of HOX genes involved in appendicular skeletal development (see work of Duboule and colleagues), there’s not yet evidence for such a thing. Alternatively, the interlocking of regulators and structural genes is so complete that disruption of the complex is prohibited.

  10. Loren Petrich says

    This reminds me of the Manx mutation in cats — Manx cats are tailless. The Manx allele (M) is dominant over its normal counterpart (m), and when homozygous (MM), it is lethal to the embryo. Thus, Manx cats are all Mm and normal ones all mm. Manx cats may have additional medical problems, like Spina Bifida.

    However there are efforts to sequence the cat genome; see this cat-genome page at the NHGRI’s list of genome targets for more. I’ve even found an effort to hunt down the Manx gene.

    I’ve also found this Yahoo Answers thread on Manx mice, which states that the Manx allele is dominant there also, and that Manx mice often have additional medical problems.

    Tracking down the Manx gene may help in working out how our simian ancestors of 30 million years or so ago had successfully stopped growing tails past the embryonic stage. Were some additional mutations in other genes needed to compensate for Manx-mutation side effects?

    It may also explain why tailless land vertebrates have been uncommon — is it difficult to stop growing tails without troublesome side effects? Would there have be selection pressure for tail absence to encourage Manx alleles to become abundant before compensatory mutations can emerge? In the absence of such pressures, it may be rare for both Manx and compensation to be present at the same time.

  11. says

    “Why does the order of genes mirror the order of body parts?”

    This is indeed one of the two Great Mysteries of the universe that, until explained by science, offer the only remaining reasonable chance that there is a god who designed it all!!!

    The other Great Mystery is this: We know that radioactive isotopes decay at a certain average rate, but whether or not one particular atom is going to decay now or later is simply now discernible by any attribute of that atom that we can see.

    God is obviously very orderly. The Hox genes are a list of things to do to build an animal! It is wondrous!

    On the other hand, it seems that god does indeed play dice with the universe, as indicated by the radioactive isotopes. God is fickle and random in a wondrous way!

    But, no, god is very orderly, because the hox genes could not for any other reason be the way they are….

    Yet, the randomness of the radioactive iso…

    wait, wait there IS an explanation for it all!!!!!

    There are TWO gods. One orderly, the other messy!! It is Wondrous!

    Its like the odd couple. Felix and Oscar. Felix and Oscar are the god(s).

    Wow. In just a few moments I went from being an atheist to being a duotheist. I feel kind of light headed now …

    …. Praise Felix. And Oscar.

  12. Benjamin says

    Loren said, “Tracking down the Manx gene may help in working out how our simian ancestors of 30 million years or so ago had successfully stopped growing tails past the embryonic stage.”

    As far as I can tell, Manx cats do not grow their tail (or just a stub). In our case, we actually have a “tail” (the coccyx). It’s just very small and doesn’t protrude out of our bodies. Let me know if I’m off base here – I’m an engineer, not a biologist.

  13. Sivi Volk says

    Wow, that was great. Neither of my genetics classes did anything more than mention Hox genes – I knew they influenced morphology, but it’s nice to have it laid out so clearly. This post isn’t just useful for laypersons; it’s clearer than many of my textbooks.

    So, er, I second #11.

  14. Leukocyte says

    The textbook “From DNA to Diversity” by Carroll, Grenier and Weatherbee is a great source for not only hox genes, but many of the other gene regulatory logic that is involved in body plan formation… for those of you that had a bad textbook.

  15. William Knight says

    Are there any good software programs or tools that one could use to represent and simulate the morphological activity of Hox genes?

  16. Espahan says

    Thank you for a very clear and informative post on hox genes. What a fasinating subject. I learn something new every time I come here. Last year I wouldn’t have known the difference between a Hoax and a Hox.

  17. SEF says

    It’s just very small and doesn’t protrude out of our bodies.

    Usually! But this site seems to have collected together more images of human tails in one place than I’ve seen before elsewhere (though the text might not be as good). A quick search didn’t turn up the better sites I’d come across previously. Here’s another though:
    http://www.thefetus.net/page.php?id=997

  18. Stephen Wells says

    Fantastic post, as always. Reading Pharyngula is what allows me (a mineral physicist by background) to bluff my way in life sciences groups.

  19. hoary puccoon says

    If teleost fishes have 7 or 8 Hox genes, how relevant are the studies of zebra fish to other vertebrates? Does that mean the studies of human-like Hox genes must be done on other mammals? (I’m assuming most can’t be done on human embryos for ethical reasons.)

    I’d love to see another post on zebra fish development, compared and contrasted with both insects and mammals.

  20. Torbjörn Larsson, OM says

    As far as I can tell, Manx cats do not grow their tail (or just a stub). In our case, we actually have a “tail” (the coccyx).

    While I now appreciate the difficulties with transforming or deleting segments, I was thinking the same. But according to the infallible Wikipedia, Manx cats fall all along the scale between normal to “tailless”, and is classified accordingly.

    The references seems to bear most of that out (but the tail length of a “Longy” isn’t specified more than “visible short”), and also suggests that different spinal defects that can be observed stems from when the gene action happen to affect the spine above the tail.

    But cats can be stably “tailless” as well, Lynx comes to mind. Also, I can think of several groups (or whatever) that have some at least superficially “tailless” species. (Turtles, rodents, et cetera.)

  21. Torbjörn Larsson, OM says

    As far as I can tell, Manx cats do not grow their tail (or just a stub). In our case, we actually have a “tail” (the coccyx).

    While I now appreciate the difficulties with transforming or deleting segments, I was thinking the same. But according to the infallible Wikipedia, Manx cats fall all along the scale between normal to “tailless”, and is classified accordingly.

    The references seems to bear most of that out (but the tail length of a “Longy” isn’t specified more than “visible short”), and also suggests that different spinal defects that can be observed stems from when the gene action happen to affect the spine above the tail.

    But cats can be stably “tailless” as well, Lynx comes to mind. Also, I can think of several groups (or whatever) that have some at least superficially “tailless” species. (Turtles, rodents, et cetera.)

  22. says

    Lovely! Hurray for Hox genes!

    Loren Petrich, like others I’m wondering where Manx cats with intermediates between completely tailless and long tails fit in. The mendelian genetics proposed seem far too simplistic to explain the variants actually observed.

    And speaking of domestic animals, how much research has been done on the dog genome? Would be interesting to see an explanation to why dogs are so incredibly variable when a cat is a cat is a cat!

  23. says

    And speaking of domestic animals, how much research has been done on the dog genome? Would be interesting to see an explanation to why dogs are so incredibly variable when a cat is a cat is a cat!

    At least part of that is probably because humans have spent a lot less time trying to breed freakishly mutated versions of cats for all occasions ;)

  24. says

    greg laden: I believe you should check out Discordianism. Although Eris, goddess of discord and of things that exist, is our main deity, we also accept the existence of her sister Aneris, goddess of order and of things that do not exist.

  25. WuffenCuckoo says

    I recently read “The Regulatory Genome” by Eric H Davidson, which deals largely with HOX genes. I am not a biologist, and I found it to be fascinating. Highly recommended.

  26. Biggboy says

    Interesting stuff indeed. I am a radiologist by trade, and over the 30 or so years I have spent staring at X-rays I have been struck by the anatomic variation found in completely functional bodies.

    Some variations in the axial skeleton reflect a more generalized genetic abnormality, in Down’s syndrome for example a frequent association is only 11 pairs of ribs (rather than 12) together with a range of cardiac anomalies. Much more common and benign is variation such as cervical ribs or only 4 lumbar vertebrae.

    The interesting thing insofar as it relates to Hox gene expression is that the cervical ribs can range from small attenuated stubs all the way to full fledged ribs that are fully integrated into the anatomy of the thoracic inlet. Additionally the absence or presence of these ribs can be unilateral, or if bilateral seen as very asymmetric structures. Similarly fusion between L5 and S1 can vary in degree bilaterally as well as by unilateral extent.

    I lay no claim to any genetic expertise but would be fascinated to hear of possible mechanisms in Hox expression that could explain the asymmetries.

  27. Steviepinhead says

    Superb, PZ: thanks!

    Also, thanks to the commentators for the thought-provoking discussion (and illustrations) of Manx-ness versus tailedness (and tail-lessness) in humans and other species.

    And for the book recommendation (Davidson’s Regulatory Genome)…

    You folks (Peezeelians? Pharyngulites?) are awesome!

  28. says

    Thanks for another excellent Hox post. My significant other is making a presentation to an introductory-level college biology class on Hox genes; does anyone here have some good sources for her to use? I think I’ve dug up all the Hox posts that PZ has made, plus “The Fruit Fly’s Tale” from The Ancestor’s Tale.

  29. rouli says

    “The obvious hypothesis is that there’s an LCR that controls the expression of each HOX cluster”

    what’s LCR?
    and while I’m asking stupid question, what makes the hox genes themselves express in the specific places they are expressed in? That is, why, for example, is lab expressed in the head? What’s the reason for the head-tail orientation?

  30. Steviepinhead says

    LCR: my guess is Locus Control Region.

    What’s that mean? Beats me, but I’m sure one of our less-pinheaded commentators can elucidate further!

  31. oceans 111 says

    I’m interested in whether this segmentation also occurs in the soft tissues – if you get enough extra thoracic ribs, do you get another lobe of lung, for example?

  32. Owlmirror says

    (@#42): I think Sean B Carroll’s Endless Forms Most Beautiful has lots of introductory-level stuff on Hox and development in general. There may be too much detail in some parts, but I figure some good examples could be selected from the text.

  33. Steviepinhead says

    oceans 111:

    if you get enough extra thoracic ribs, do you get another lobe of lung, for example?

    Hmm, extra ribs and “lobolung.” I could definitely, um, wolf that down!

  34. Stevipinhead says

    Okay, okay. Since I was overwhelmed by requests, not to mention by my own infrequent bout of curiosity, I now offer this definition of Locus Control Region, courtesy of answer.com:

    locus control region (¦lō·kəs kən′trōl ′rē·jən)
    (genetics) A segment of DNA that controls the chromatin structure and thus the potential for replication and transcription of an entire gene cluster, such as the beta-globin cluster in vertebrates.

    Now you know everything I know about LCR.

    Fortunately, I do have a vague, pinheaded recollection of what chromatin is, courtesy of that Jablonski person…

  35. Joel says

    “I’m interested in whether this segmentation also occurs in the soft tissues – if you get enough extra thoracic ribs, do you get another lobe of lung, for example?”

    In the cases I’m familiar with, loss of HOX genes leads to a reduction or loss of organs found at the level of the axial body plan at which that HOX gene initates expression (the most rostral position). Presumably, this reflects HOX gene expression in the somites, from which the cells migrate to give rise to the organs at that level.

    Short story: I can’t think of any examples of homeotic transformation of soft tissues that mirror the homeotic skeletal transformatin in the axial body plan. It’s more like the appendicular skeleton, where loss of HOX gene expression causes a simple loss of structures.

    BTW, LCRs seem to function as kind of “super-enhancers” that control a cluster of related genes, often in a developmentally programmed sequence. There is an LCR for, e.g., the beta globin gene cluster that insures that the sequence of embryonic, fetal and adult beta globin genes are turned on (and off) in the correct temporal sequence.

  36. harold says

    This was a great article.

    The question about what evolutionary pressure would account for a regular sequence that happens to be mapped onto chromosome geometry in a way that mirrors body phenotype geometry is fascinating. I can’t think of an obvious explanation.

    It did provoke me to wonder if unicellular organisms have hox gene clusters at all, which led to to this nice link –

    http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1891803

  37. harold says

    In the mouse, it’s obvious why there is selective pressure to maintain the mapping of Hox genes on the chromosome – they work together, so naturally, at a physical level, it facilitates co-expression when they are contiguous along the chromosome.

    In the fly, where they seem to be expressed individually, it is less clear why order should matter.

    Could very early hox-ordered lineages have actually made use of coexpression/redundancy, and the fly be from a lineage that paired down that redundancy?

  38. Barn Owl says

    RE: the Manx cat discussion-

    Perhaps the T-box/Brachyury genes would be better candidates to explain the spectrum of tailless/short-tailed phenotypes in Manx cats. Classic T/brachyury genetics investigations began in the 1930s; surely someone has looked into this in Mus musculus’ mortal enemy, the domestic cat. I’m just not having a good PubMed day myself. ;-)

    Genes involved in regulating taillessness in ascidian larvae have clever names such as Manx, bobcat, and Cymrian…for lucid descriptions of T-box transcription factors and ascidian embryo patterning, check out the aforementioned Davidson book, as well as his earlier Genomic Regulatory Systems.

  39. Steviepinhead says

    Harold, thanks for the great link.

    I particularly recommend Fig. 1 of the linked article (without at all wanting to discouraging anyone from reading the whole thing!): altho PZ has published similar info in a somewhat different format, this graphic nicely parallels the usual “tree of life” (at least the multicellular plant-animal twig thereof). It nicely condenses several rebuttals of creo canards into one handy package: mutations do give rise to new info and complexity, etc.

    Thanks again! Another great example of sharing the wealth of knowledge available here.

  40. harold says

    Stevie P –

    Thanks. That is pretty funny. The FSM sure worked her butt off, designing it to look exactly like evolution in every possible way. Talk about detail oriented.

    A couple more observations –

    1) Although brief and highly speculative, the cancer stuff at the end is quite interesting. In my old career as a diagnostic pathologist I could rattle off all the common translocations associated with the various subtypes of leukemia and lymphoma (their use in classification is ahead of their use in understanding of pathophysiology and targeted treatments for the time being).

    2) From a broader perspective, think about this – plants are just as multicellular and complex as animals, and develop from tiny embryoes to giant trees, but they lack a hox gene cluster. They obviously use some kind of different mechanism(s) for similar functions, since they have a lot of morphologic specialization. Pretty interesting. I was interested in nervous systems and brains as an undergrad, and then I went to med school, so I am quite ignorant of plant biology.

  41. Joel says

    The specification of segment identity within flowers is controlled by MADS-box proteins which, like HOX proteins, are a family of structurally related transcription factors. MADS-box proteins are structurally unrelated to HOX proteins but mutations in their genes lead to homeotic transformations, like mutations in HOX genes.