Notes

genes & development

development - process in which a fertilized egg undergoes multiple rounds of cell division to become an embryo /w specialized tissues & organs

differentiation - the process where gene regulations allows cells to beocme specialized

genetic basis of development - jhow does a single fertilized egg become a complex multicellular organism?
(insert slide 3 picture)

totipotent cells
a human egg is fertilized in the fallopian tube, becoming a zygote; the fertilized egg is totipotent (can give rise to a complete organism & the membranes that support a developing embryo)

formation of the morula
-the zygote travels to the uterus, undergoing cell divisions as it travels to form a ball of cells called the morula; once the morula reaches the uterus interior, a few thousand cells rearrange themselves, forming a hollow sphere called the blastocyst

formation of the blastocyst
-a group of cells form the inner cell mass attached to the interior wall of the blastocyst, which is where the body of the embryo develops
-the cells of the inner cell mass are pluripotent (the cells can give rise to any other cell type in the body, but not an entire organism)
-cell division continues & the blastocyst continues to grow & divide

embryonic tissue layers
-the blastocyst is implanted in the uterine wall & the multiplying cells of the inner cell mass reorganize to form a gastrula, where the 3 germ layers (sheets of cells that develop into specific cell types) are established:
a) ectoderm - becomes epithelial, pigment, and nerve cells in the brain
b) mesoderm - makes up the inner layer of skin, muscle cells, & red blood cells
c) endoderm - includes cells of the linings of the digestive tract & lungs & liver & pancreas cells

embryonic stem cells
-found in the inner cell mass; pluripotent, can give rise to any of the 3 germ layers
-cells further along in differentiation are multipotent (can form a limited # of types of specialized cells)
-cells of the germ layer are multipotent bc they can only give rise to cell types specified for each germ layer
-totipotent, pluripotent, & multipotent cells are all stem cells (capable of differentiating into different cell types)

stem cells lose their ability to beocme any type of cell through changes in gene expression; when cells comit to a particular developmental pathway, unecessary genes are turned off & are difficult to turn back on

gurdon's experiments:
-transferred nuclei from differentiated cells into unfertilized eggs whose nuclei had been inactivated /w uv light (nuclear transfer)
(insert slide 14 pic)

-differntiated nucleus is able to reporgram itself in the egg & differntiate again into all the cells of a tadpole; nucleus of an intestinal cell & cytoplasm of the unfertilized egg can support complete devlopment of a normal animal
-cells further along in differntiation are mroe difficult to reporgram
-when nuclear transfer succeeds, the result is a clone (indiviudal that carries and exact copy of the nuclear genome of another individual)
(insert slide 15 pic)

stems cell play a prominent role in regenerative medicine (aims to use the natural processes of cell growht & development to replace diseases/damaged tissues)
-bone marrow transplants
-parkinsons disease
-alzheimers disease
-heart failure
-diabetes
-burns/wounds
-spinal cord injuries
-stem cells can be used to regenerate diseased/damaged tissues: reprogrammed cells, called induced pluripotent stem cells (iPS cells) or pluripotent embyronic stem cells

drosophila lfie cycle
(insert slide 20 pic)
-gene regulation during development is hierarchical (genes expressed early in development influence the expression of genes later in development)
-gastrulation - cells of the blastoderm migrate inward, creating layers of cells within the embryo; causes segmentation of the embryo

maternal effect genes
(insert slide 22 pic)
-genes (such as bicoid & nanos) that are expressed by the mother but affect the phenotype of the offspring (larvae); bicoid mutants lack anterior segments while nanos mutants lack posterior segments

gradients
(insert slide 23/24/25)
-after fertiliztion, the zygote produces the bicoid & nanos proteins from the maternally derived mRNAS; the protein gradients resemble the mRNA gradients
-bicoid mRNa & protein is localized in the anterior of the egg while nanos mRNa & protein is concentrated in the posterior end
-as translation of the mRNAs of bicoid & nanos occurs, the proteins will inhibit the expression of caudal & hunchback respectively

-genes controlling development are turned on in groups & each successive groups acts to narrow the pattern od differentiation; after maternal effect genes, 3 other class are expressed in the hierarchy:
a. gap genes (insert slide 27)- refien the anterior-posterior gradient established by maternal effect genes; affect the development & differentiation of groups of segments in the embryo; produces transcription factors that control the pair rule genes
b. pair rule genes (insert slide 28)_- help control the development of the alternating 7 stripes in the larva; produces transcription facotrs that control the segment-polarity genes
c. segment-polarity genes (insert slide 29)- each of the 7 sections is divided into 2 /w a posterior & anterior section

Hox genes
gap, pair rule, & segment-polarity genes control the pattern of expression in homeotic (Hox) genes (genes that identify where boyd parts or segements will develop in the embryo)
Examples of mutations in homeotic genes: Antennapedia mutants develop legs where antennae should be & bithorax mutants develop two sets of wings instead of one set
(insert slide 34)
-the drosophila genome contains 8 Hox genes comprising 2 lcusters: the Antennapedia complex & the Bithroax complex; the genes are arranged along the chromosome in the same order as their products function in anterior-posterior segments along the embryo
-the amino acid seuences of the DNA-binding domains (homeodomains) of Hox gene products are similar from one organsim to the next
-mammalian Hox genes are important in embyronic development of structures that becomes parts of the hindbrain, spinal cord, & vertebral column

evolutionary consevration
-molecules that are similar in sequence among distantly related organisms are evolutionary conserved

Pax6: a master regulator of eye development
-eye only evolved once: presence of same lgiht-sensing molecule (opsin) in all eyes usggest it was present in the common ancestor & the Pax6 gene is found in many organism & mutations in it cause developmental defects in the eyes

loss-of-function mutation: mutation that inactivates the normal function of a gene
gain-of-function: a mutation in which a gene is expressed in the wrong place or at the wrong time

-when Pax6 from mice was introduced to fruit flies, fruit fly eyes still developed instead of mouse eyes because the fruit fly genome didn't have the genes needed to make mouse eyes & becuase of the downstream genes affected by Pax6 (genes that function later in the process of eye development)

combinatorial control (regulation of gene transcription according to the mix of transcription factors in the cell)
(insert slides 43/44/45)

cell signaling & development
(insert slide 46)

apoptosis - programmed cell death; some cells must die to dvelop or maintain a structure; the cell recieves a signal from within or outside the cell triggering an irreversible cell death pathway