Lecture 9 - Dorsoventral axis inversion and Hox genes

Question 1

How was the idea of Dorsal-ventral axis inversion first proposed between vertebrates and invertebrates?

Answer 1

Geoffroy St Hilaire (1822)

• lobster protosome similar anatomical orgnaisation to a vertebrate deutrosome but that the dorso-ventral axis was inverted
• ventral side of the lobster was homolgous to the dorsal side of the vertebrate
• may have a common origin

Question 2

What evidence supports the dorso-ventral axis inversion hypothesis?

Answer 2

-Drosophila has dorsal heat and ventral nervous system
-drosophila homolog of chordin is sog
-drosophila homolog of BMP4 is Dpp
Opposite pattern of expression is shown BMP4 and Sog
-In vertberates BMP signalling requires for ventral structures/insects BMP signalling required for doral structures
-Similar neurogenic organisation expressed in three terratories along dv axis
Therefore during the evolution of protosome and deutrosomes form the common bilateral ancestor, the dorsal-ventral axis has been inverted

Question 3

How does the nervous system support the dorso-ventral axis inverion?

Answer 3

Invertebrates
-early nervous system of drosophila is divided into three terratories along the dorsal ventral axis which express certain transcription factors
-Most dorsal = msh - muscle segment homeobox], ind - intermediate neuroblast defective, most ventral = vnd - ventral neuroblast defective
Vertebrates
-primary nervous system of the Xenopus is also divided into three terratories along the dorsal ventral axis
-amphibian orthologs of msh, ind, and vnd
=> msh/msx (sensory neurons), ind/gsh2 (intermediate neurons, vnd/nkx6 (motor neurons)

• Three domains have been conserved in the order of expresssion in deutrosome and protosomes
• terratories express the same set of homeobox genes
• but in the opposite side of the embryo
• Ventral - fly
• Dorsal - Amp

Question 4

By what process can the genes expressed at certain times in an embryo be illustrated?

Answer 4

In situ hybridisation

Question 5

What are the features of Hox genes?

Answer 5

• code for homeodomain transcription factors
• present in all bilaterally symmetrical animals
• expression of hox genes at particular levels along th eAP axis defines segment identity
• show chromosomal clustering = hox genes are physically linked within the genome in linear arrays
• colinear expression = when are where a particular hox gene is expressed in the embryo depends on its position in the hox gene cluster

Question 6

How are hox genes and the pattern the AP axis conserved in vertebrates/invertebrates?

Answer 6

• Anterior-posterior axis is highly conserved
• Mouse embryo has 4 hox gene clusters that show the same linear expression of hox gene orthologs to drosophila
• During vertebrate evoltuion relative to the last common ancester there have been 2 rounds of genome duplication

Question 7

How are Ubx and AbdA involved in the evolution of arthropod limbs?

Answer 7

• Ubx and abdA form the 5’ end of the hox gene cluster
• in arthropods the distaless (DII) gene is required for leg outgrowth - may have been involved in regulating leg numbers in different arthropod groups
• in insects Ubx and AbdA hox genes repress the expression of DII and leg development in the abdomen
• in situ hybridasation shows that in the developing drosophila embryo DII expression is shown in T1, T2 and T3 not in the anterior sections
• when Ubx and AbdA are knocked out of the triphoteon bug this negatively regulates the expression of DII and results in ectopic growth of additional legs

Question 8

What does the action of Ubx and AbdA in flies and the supression of DII suggest about the evolution of Arthropoda (drosophila, Crustacea) ?

Answer 8

• changes in the activity of Ubx protein have contributed to the divergence of arthropod body plans
• in drosphila Ubx is expressed in the abdomen and excluded from the thorax which bears the limbs
• however, in crustacea Ubx is expressed in teh leg forming region

Question 9

What is the difference in the action of Ubx and AbdA between drosophila and Crustacea? And what does this suggest about the evolution of leg number in the arthropods?

Answer 9

• in drosphila Ubx is expressed in the abdomen and excluded from the thorax which bears the limbs
• however, in crustacea Ubx is expressed in teh leg forming region
• Ubx protein from crustacea and the primitve arthropod Onychophora does not repress distaless expression in flies (gene swap experiment)
• suggests that the aquisition of distalless repressing activity in Ubx may have been important in the evolution of leg number in the arthropods

Question 10

Why are Hox genes thought to have an ancient origin?

Answer 10

Present in all bilaterally symmetrical animals but also pattern the axes of non-bilaterally symmetrical animals e.g. Hydra

• Although they lack a genuine anterior posterior axis (no gut opening) they still show the same kind of clustered organisation of hox genes
• controls patterning along the main body axis

Question 11

What is ubilateria?

Answer 11

The last common ancester of all bilaterally symmetrical organisms

Question 12

What do we can we assume about ubilateria?

Answer 12

• defined head to tail axis
• defined dorsal ventral axis
• probably some form of appendage (dll expressed along projection of structures along the main body axis)
• defined anterior-posterior axis
• photo receptor at the anterior end (pax6)
• circualtory pump (homolog of tinman gene in regulating structure)
• segmental identity along the AP axis (Hos gene homologs)
• patterning along the dorsal ventral axis (interaction between TGFβ homolog and repressor of nervous system patterning)