T2 Shimeld- Principles of animal development + Development and diversity

how is the oocyte initially divided in most bilaterian animals?

• most animals undergo holoblastic cleavage

• bilaterians typically go through three initial divisions

• polar bodies (small cells with a discarded nucleus) determine the top

• radial cleavage is seen in deuterostomes, where the three divisions are perpendicular

• spiral cleavage is often seen in protostomes (ecydosozoa + lophotrochozoa)- the third division is twisted, and the divisions may be equal or unequal, to produce different cells

• some species, eg. teleost fish, undergo teleoblastic (instead of holoblastic) cleavage, where cleavage is restricted to just part of the egg due to a high amount of yolk

what is the blastula?

• bilaterian animals enter a blastula stage during early development, where the zygote has a fluid-filled blastocoel space in the middle surrounded by a layer of cells called the blastoderm

• this undergoes gastrulation to move cells into the blastocoel

• this produces three cell layers: the ectoderm, mesoderm and endoderm

• this movement of cells is an example of morphogenesis (another being neural crest cell migration)

what are the three processes involved in development in animal cells?

• differentiation- expression of different transcription factors that activate certain groups of genes (eg. myogenic genes controlled by MyoD) and repress others

• pattern formation- lineage dependent mechanisms (programmed asymmetric cell division) + organising fields of cells (using intercellular signalling/morphogen gradients- Wolpert’s french flag model eg. maternal bicoid with mRNA localised at anterior + protein diffusion gradient)- along the three embryo axes, in many cases using particular intermediate Hox genes that encode homeodomain TFs

• movement/morphogenesis- gastrulation + neural crest cell migration

what are the two main routes to identifying the genes that control animal development?

biochemistry:

• studying compounds that have been extracted from tissues

• this relies on fractionation and repeated assay to identify the protein

• this works best with intercellular signalling systems, because they can be applied topically

• not very useful with intracellular proteins/TFs

forward genetics:

• observing the phenotype change from a mutant genotype

• most of the genes identified were either for transcription factors or intercellular communication

• these are very highly conserved across animal species (ancestral trait)

how do embryonic axes get determined in animal development?

• A/P signalling is controlled by Wnt localisation

  • bilaterians- Wnt localised at the posterior end

  • non-bilaterians- Wnt localised at the oral end (they have an oral/aboral axis)

• D/V signalling is controlled by Bmp localisation

  • deuterostomes- at the ventral side

  • protostomes- at the dorsal side

  • this is developmentally equivalent, mostly due to our labelling of dorsal and ventral according to gravity

how did the developmental gene toolkit evolve?

• tandem gene duplication- during meiotic recombination, mistakes in crossing over cause one chromosome to have two copies of a section of DNA, while the other has none

  • lack of the DNA is likely to be fatal in the inheriting offspring

  • however the extra copies aren’t necessarily deleterious in the resulting offspring (leads to copy number variants)

• whole genome duplication occurred twice in early vertebrate evolution

these events lead to redundancy

• these permit the evolution of genes with new developmental functions by mutations (because redundancy means the mutation doesn’t affect the other copy of the original gene)

  • eg. changing the amino acid sequence of the homeodomain of Hox genes changes the DNA sequence it binds to

• how the gene is expressed in different cells can also be changed

  • eg. changing the position of a particular Hox gene changes how far along the A/P axis the corresponding trait is expressed

  • repurposing of genes for new functions, eg. using Hox genes to control limb patterning

  • mutations in gene enhancers can affect gene expression eg. to allow binding of a new TF, prevent binding of an existing one, or create a new enhancer region for a TF