1. Development: Cell Division, Cell Differentiation, and Morphogenesis
Cell Differentiation – change in pattern of gene expression (gene expression profiles)
Morphogenesis –change in shape (creation of form)
Cell Differentiation to specific cell fates: capacity to differentiate into different types of cells
Totipotency to less than totipotent
Differentiation occurs in stages: totipotent cell; stem cell with restricted potency; terminally differentiated cell capable of giving rise only to other cells of the same type
Variable gene activity theory: differentiation is a result of limiting the gene expression profiles of cells with the same genome
Dedifferentiation: return to totipotency – required for animal cloning (sheep mammary cell nucleus used to clone Dolly)
Cell Differentiation is due to intracellular and extracellular signals
Specific subcellular localization of Intracellular signals
leads to asymmetric cell divisions, daughter cells have different gene expression profiles
Specific extracellular signals determine a cells pattern of gene expression
Change in gene expression profiles
Coordinates gene expression profiles of neighboring cells – common cell type, common tissue type…
Both types lead to Determination
When cell is committed “irreversibly” to a particular fate or set of fates
Types of developmental decisions:
Binary decision: cell adopts one of two alternative (mutuallly exclusive) cell fates
Germ line versus soma
Male versus female
Decision among multiple options
Determination of cell’s fate within one of the main axes of the body
Anterior – Posterior
Dorsal – Ventral
Left - Right

2. Levels of Control of Gene Expression

3. Cell Differentiation: A Binary Switch
Intracellular Signals
Asymmetric subcellular localization
Extracellular Signals
cell-to-cell contacts
paracrine signalling
Master Switch is usually one or two genes that are directly regulated by the signal
Example Binary Switch Mechanisms: Sex determination in Drosophila melanogaster and Homo sapiens
Signal is the ratio of X chromosomes to autosomes in Drosophila
Signal is the presence of a Y chromosome in humans
Mater switch = Sxl in flies; SRY (sex reversal gene) also known as TDF (testis determining factor) in humans

4. Sterile male Klinefelter Syndrome Turner Syndrome
Drosophila sex is determined by the ratio of the number of X chromosome to number or sets of autosomes
In Human, sex is determined by presence or absence of an intact Y chromosome
Drosophila is diploid, with n = 4
3 autosomes = 1 “autosome set”, 1 sex chromosomes
XX female 2 sex chromosomes, 2 autosome sets = X/A = 1
XY male X/1 = ½
XXX AAA triploid X/A = 1; female
XYY AAA triploid X/A = 0.3; male
XXY AAA triploid X/A = 0.67; intersex
Klinefelter Syndrome
Turner Syndrome
Sterile male

5. Also some activation Also some activation of male-specific
Fly Sex determination: Overall pathway through Sxl
Sxl activation in early female development = transcriptional control
Maintenance of Sxl expression later in female development is due to regulation alternative pre-mRNA splicing
Regulation of tra and dsx = regulation of alternative splicing
Also some activation
of male-specific
genes
Also some activation
of female-specific
genes

6. Signal = X chromosome/Autosome Ratio

7. Signal Activates “Early” Promoter of Sxl
X/A = 1
NUM > DEM
X/A = .5
NUM < DEM

10. LOSS OF FUNCTION MUTANT PHENOTYPES
XX male phenotype
(Lethal)
Viable
XX male phenotype
Viable
Intersex
Intersex
Fly Sex determination: Overall pathway through Sxl
Sxl activation in early female development = transcriptional control
Maintenance of Sxl expression later in female development is due to regulation alternative pre-mRNA splicing
Regulation of tra and dsx = regulation of alternative splicing

11. Another aspect of sex determination: Dosage Compensation
Human dosage compensation: decrease expression from XX females by X chromosome inactivation
Flies: increase expression from XY or XO males by expression of transcriptional activators
Is why sex-lethal is a female lethal - XX sxl mutants overexpress genes on both X chromosomes – imbalance in gene expression
Dosage compensation probably acts through Sxl…