genomic equivalence and early patterning

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Genomic Equivalence and Early Patterning

Readings

y Chapter 19

o p.429 Is cell differentiation reversible? To p.435 Differential

gene transcription is a hallmark«

o p.442 In the fruit fly, « and maternal effect genes

Does loss of cellular potential correspond to loss of genetic

information?

Plant cells seem to be totipotent



What about animal cells?

Nuclear Transf er 1950s (Briggs & King)

y No information is lost from

the nuclei of cells as they

pass through the early

stages of embryonic

development (Principle of

Genomic Equivalence)

y The success of cloning by

nuclear transfer approached

zero when donor nuclei from

older developmental stages

are used

But what about adult animal cells?



y Totipotency can apparently berescued from adult animals

cells (Dolly)

y Nuclear transfer in other

mammals since Dolly

y Nuclear transfer, combined

with embryonic stem cell

technologies, could

individualize regenerative

medicine

y Nuclear transfer, combined

with embryonic stem cell



technologies,

could

individualize

regenerative

mediciney Can we rescue

embryonic

potential from

adult cells

without

cloning?

y http://www.sciencemag.org/cgi/content/full/318/5 858/1917

and

y http://www.cellpress.com/misc/page?page=misc 21

y Over 300 stories about the research appeared online within 2 hoursafter being posted, with nearly 800 stories by 3pm that day.

y Cloning animals from differentiated somatic cell nuclei tells us that

no genomic information (genes) is lost as cells differentiate.

y Instead, cell differentiation relies on the selective use of the genetic

tool kit (can turn genes within the cell on or off).

y Differential gene expression is a hallmark of cell differentiation.

y www.associatedcontent.com/article/110337/clo

ning_horses_takes_steps_forward.html

y www.vet-stem.com

Commercial Livestock Cloning



y www.viagen.com

y There is no zygotic/embryonic gene expression during early

development (some or most of the cleavage stage, depending on

the organism)

y Early development is controlled by maternal information in theform of proteins and mRNAs

y These cytoplasmic determinants are not uniformly distributed in

the oocyte

y The effects of maternal cytoplasmic determinants on early

patterning of the embryo

Genes that Regulate Development in an Embryo

Five processes that contribute to development

y Determination: seals the fate of an embryonic cell

y Differentiation: the process by which different types of cells arise

y Patterning: defining the orientation of an embryo and its tissues

y Morphogenesis: the shaping of the body and its organs

y Growth: increase in size by cell division

The Body Axes

The gray crescent in the amphibian zygote results f ro movements of cytoplasm in the

f ertilized egg cell



Important cytoplasmic determinants are resent in the gray crescent



The gray crescent in the amphibian zygote corresponds to the f uture dorsal side of the

embryo



The dorsal-ventral axis of the f rog blastula appears to be established by the

asymmetrical distribution of the protein -catenin



-catenin is selectively degraded on one side of the embryo

Genetic screens, done during the 1970s, identif ied most of the developmental control

genes that pattern the Drosophila embryo

Maternal Eff ect Genes in Drosophila

y Are expressed in nurse cells in female ovary



y Transcripts (mRNA molecules) are transported into specific regions

of the oocyte cytoplasm

Maternal Eff ect gene transcripts (mRNAs) are translated into transcription f actors

after f ertilization to establish protein gradients

y The bicoid

messenger RNA

stimulates head-

specifying genes

and 19.14

illustrates

development of the

anterior-posterior

axis and

segmentation due



to three other types of genes

y There is also a posterior protein gradient in the Drosophila oocyte

Maternal gene products def ine an anterior and a posterior end of the embryo

Bicoid mutant has two tail ends

y Bicoid and Nanos are both RNA

binding proteins

y By binding to specific sequences

in mRNA molecules they regulate

translation of their target

mRNAs

y Bicoid binds to a specific

sequence at the 3¶ end of the

Caudal mRNA and prevents

translation initiation factors from binding to the 5¶ end

y Translation repression of Caudal by Bicoid sets up complementary

gradients of anterior and posterior determinants

y Bicoid can also bind to DNA.

y By binding to specific sequences in the regulatory regions of genes

it regulates transcription, too.

y Many developmental regulatory proteins are multifunctional

genomic equivalence and early patterning

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