Development Gen

7/29/2019 Development Gen

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Development

Development is a program of regulated growthby which a multicellular organism is formed froma single-cell, the zygote.

The developmental program results frominteractions between genetic regulation andenvironmental influences.

Regulated developmental processes include

cellular proliferation, cellular determination and differentiation, cellular migration, and cell death.


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Stem Cells and

Differentiation The fertilized egg or zygote

is totipotent able to createdaughter cells capable ofserving any role.

Stem cells are pluripotentable to create daughter cellsthe can differentiate intomany, but not all, cell types.

Just as important as theirpotential is the fact that

stem cells and less potentprogenitor cells canproliferate, replenishing theirnumbers.

Differentiated cells arespecialized to perform aspecific function.


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Determination of Cell Fate

Determination is agraded limitation ofthe fate of a cell andits progeny.

Determination is agenetic regulatoryevent, and it precedesdifferentiation, oftenby many cellulargenerations.


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Body Axes


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Drosophila

Development The fruit fly Drosophila

melangasterhas been used as

model organism to studyanimal development for almosta century.

It is easy to care for.

It has a short generation time. It has a low chromosome

number, N= 4, three autosomesand one sex chromosome.


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Early Drosophila Development

After fusion of the male and female haploid pronuclei, the diploidzygotic nucleus undergoes nine mitoses, giving rise to amultinucleate syncytium.

By the seventh mitotic cycle, nuclei at the posterior pole are alreadydetermined to be the precursors of germ tissue.

Nuclei migrate to the periphery, and over the following four mitoticcycles, cytokinesis occurs, giving rise to a cellular blastoderm.


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Maternal Effect Genes

Maternal effect genes are developmentallyimportant genes expressed by cells of themother during oogenesis.

The products of these genes determine thepolarity of the egg and, therefore, the body axesof the embryo.

The products of these genes are morphogens,

proteins that convey positional information andregulate development. These proteins can betranscription factors, translational repressors,receptors, or cell-adhesion molecules.


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Maternal mRNAs act as morphogens.

From the mothers diploid genotype, mRNA is transcribed and depositedinto the egg cytosol. mRNA for the gene bicoidis localized in the anterior of the egg. mRNA for the gene nanosis localized in the posterior of the egg.

mRNA for the gene caudalis distributed evenly. In the cells of the early embryo, these mRNAs are translated.

Bicoid protein is a transcription factor regulating many developmentallyimportant genes of the head and torso. It is also a translational repressor ofcaudal mRNA.

Nanos protein is a translational repressor. It affects the translation of mRNA forthe gap gene hunchback (hb).

Caudal protein is a transcription factor that regulates many genes involved indetermination of abdominal structures.


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Plasma membrane proteins also

convey positional information. Maternal effect genes can also code for transmembrane

receptors and cell adhesion molecules that aredistributed evenly over the surface of the early embryo.

Maternal follicular cells, which surround the egg andearly embryo, provide ligand for these receptors inspecific areas, helping determine the embryos bodyaxes. The receptor Torso is exposed to its ligand (possibly a maternal

protein called trunk) on each terminal pole of the

anteroposterior axis. The receptor Toll is exposed to its ligand (a Spatzle peptide)

only along the ventral surface. The receptor Gurken is exposed to its ligand (Torpedo) only on

the posterior and dorsal surfaces.


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Mutational Analysis of Maternal

Effects Since these genes are maternal effectgenes, it is important to remember thatthe phenotype of the embryo does notdepend on the embryos genotype, but onthe genotype of its mother.

A wild-type mother gives rise to normallarvae (APT in the figure). Mothers homozygous for loss-of-function

mutations for any maternal effect genecan be developmentally normalthemselves but give rise to non-viableoffspring.

Abicoid/

mother produces larvae missinghead and thoracic progenitors (PT). Ananos/ mother produces larvae missing

abdominal structures (AT). Atorso/ mother produces larvae with

abnormal head and tail development(AP).


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Segmentation Genes Segmentation genes are expressedfrom the diploid zygotic genotype of

the early embryo.

Most segmentation genes code fortranscription factors that determinethe segments of the embryo and,

therefore, the adult. Segmentation occurs as a progression

of stages. The products of maternal effect genes

regulate the expression ofgap genes.

The transcription factors encoded bygap genes (along with maternal effectgenes) regulate the expression ofpair-rule genes.

The transcription factors encoded bypair-rule genes (along with maternaleffect and gap genes) regulate theexpression ofsegment-polarity genes.


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Gap Genes

The first zygotic genes to be expressed in earlyembryonic development are the gap genes.

In Drosophila there are at least ten gap genes. Gap gene products begin determination of coarse

subdivisions of the early embryo through complex butwell-studied interactions. Krppel(Kr) and hunchback(hb) encode two transcription

factors that act in early development to determine centralregions of the embryo. In later development they play moredetailed roles in organ morphogenesis.

The genes giant(gt) and knirps(kni) also encode transcriptionfactors. They are expressed in broad bands to each side of thecentral band along the anteroposterior axis.

The gap genes tailless(tll) and huckebein(hkb) also encodetranscription factors. They act in defining the terminals of theanteroposterior axis.


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Pair-rule Genes

Pair-rule genes are expressed in an alternating bandingpattern that loosely corresponds to and helps determinethe segmentation of the embryo along itsanteroposterior axis.

There are at least eight pair-rule genes in Drosophila.Many encode transcriptional repressors. The mutualrepression of genes for even-numbered parasegmentsand genes for odd-numbered parasegments helpsdelineate boundaries.

Genes like even-skipped(eve), fushi tarazu(ftz), andodd-skipped(odd) all encode transcription factors thatinteract with those encoded by the gap genes todetermine the fates of body segments.


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Segment Polarity Genes

Segmentation is completed by the expression ofsegment polarity genes, which determine maturesegments from the parasegment pattern.

There are many segment polarity genes, whose products

serve many diverse roles. Genes like engrailed(en) encode transcription factors that

interact with those from maternal effect, gap, and pair-rulegenes to continue the genetic cascade of cell fate determination.

Genes like hedgehog(hh), wingless(wg), and decapentaplegic(dpp) encode secreted signaling peptides.

Genes like smoothened(smo), frizzled(fz), and saxophone(sax)encode membrane receptors for these signaling peptides.

Also, genes like costal(cos), dishevelled(dsh), and Medea(Med)encode proteins in the signal transduction pathways for thesereceptors.


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Mutational Analysis ofSegmentation

Segmentation gene classes arenamed from mutant phenotypesof those genes.

In each case in this figure, theareas shaded green in the

normal larva are deleted orreplaced by mirror images ofunaffected regions in themutant larva. Mutations in gap genes result in

loss of several adjacentsegments.

Mutations in pair-rule genesresult in loss of every otherparasegment.

Mutations in segment polaritygenes result in portions of eachsegment being replaced by amirror image of the adjacent

half segment.


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Homeotic Genes and Imaginal

Discs After segmentation,

homeotic genes, alsocalled selector genes, are

expressed that determinethe identity of body partsin the adult.

An imaginal disc is a

group of cells determinedto become some organ orstructure in the adult.


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Homeobox-containing genes code forhomeodomain transcription factors.

Homeotic genes have been discovered tocontain a highly homologous sequence of

about 180 bp termed the homeobox.All homeotic genes code for transcription

factors. The homeobox codes for the

homeodomain, a 60-AA helix-turn-helixDNA-binding domain.


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Mutational Analysis of Homeotic Genes

Homeotic mutations canlead to the substitution ofone body structure foranother.

For example, in this figure,anAntennapediamutanthas a fourth pair of legs inplace of its antennae.

Notice that this fly is anadult. Mutations occurringlater in the developmentalgene cascade are notnecessarily embryoniclethal.


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Hox Clusters Homeobox (Hox) genes tend to

be arranged in tandem arrays,or clusters.

The Drosophila genome has twosuch clusters, called theAntennapediacomplex and the

bithoraxcomplex. Most vertebrates, primates

included, have four suchclusters.

Interestingly, the genes alongany one such cluster tend to

exhibit spatial and temporalcolinearity. That is to say,genes along the cluster areexpressed in order with respectto time and with respect toanteroposterior position.

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