Fig µm200 µm 20 µm (a) Reproduction (b) Growth and development (c) Tissue renewal Cell division

Bacterial chromosome Chromosomes Microtubules Prokaryotes Dinoflagellates Intact nuclear envelope Kinetochore microtubules Kinetochore microtubules Intact nuclear envelope Diatoms Centrosome Most eukaryotes Fragments of nuclear envelope LE Types of cell divisions that produce identical offspring (clones) in various organisms Binary fission (prokaryotes) Mitosis (eukaryotes)

LE Origin of replication Cell wall Plasma membrane Bacterial chromosome E. coli cell Two copies of origin Chromosome replication begins. Soon thereafter, one copy of the origin moves rapidly toward the other end of the cell. Replication continues. One copy of the origin is now at each end of the cell. Origin Replication finishes. The plasma membrane grows inward, and new cell wall is deposited. Two daughter cells result.

LE 12-4 Chromosome duplication (including DNA synthesis) 0.5 µm Centromere Sister chromatids Separation of sister chromatids CentromeresSister chromatids Eukaryotic genomes are larger and more complex

LE 12-5 G1G1 G2G2 S (DNA synthesis) INTERPHASE Cytokinesis MITOTIC (M) PHASE Mitosis The cell cycle

LE 12-6ca G 2 OF INTERPHASE PROPHASEPROMETAPHASE METAPHASEANAPHASE TELOPHASE AND CYTOKINESIS 10 µm Mitosis in animal cells

LE 12-6aa Centrosomes (with centriole pairs Chromatin (duplicated) Early mitotic spindle Nucleus Nuclear envelope Plasma membrane Aster Centromere Chromosome, consisting of two sister chromatids Fragments of nuclear envelope Kinetochore Nonkinetochore microtubules Kinetochore microtubule Mitosis in animal cells

LE 12-6ba Centrosome at one spindle pole Metaphase plate Spindle Cleavage furrow Daughter chromosomes Nucleolus forming Nuclear envelope forming Mitosis in animal cells

LE 12-9a Cleavage furrow 100 µm Contractile ring of microfilaments Daughter cells Cleavage of an animal cell (SEM) Cytokinesis in animal cells

LE Nucleus Cell plate Chromosomes Nucleolus Chromatin condensing 10 µm Prophase. The chromatin is condensing. The nucleolus is beginning to disappear. Although not yet visible in the micrograph, the mitotic spindle is starting to form. Prometaphase. We now see discrete chromosomes; each consists of two identical sister chromatids. Later in prometaphase, the nuclear envelope will fragment. Metaphase. The spindle is complete, and the chromosomes, attached to microtubules at their kinetochores, are all at the metaphase plate. Anaphase. The chromatids of each chromosome have separated, and the daughter chromosomes are moving to the ends of the cell as their kinetochore micro- tubules shorten. Telophase. Daughter nuclei are forming. Meanwhile, cytokinesis has started: The cell plate, which will divide the cytoplasm in two, is growing toward the perimeter of the parent cell. Mitosis in plant cells

LE 12-9b 1 µm Daughter cells Cell plate formation in a plant cell (TEM) New cell wall Cell plate Wall of parent cell Vesicles forming cell plate Cytokinesis in plant cells

LE Experiment 1 Experiment 2 S S S G1G1 G1G1 M M M When a cell in the S phase was fused with a cell in G 1, the G 1 cell immediately entered the S phase—DNA was synthesized. When a cell in the M phase was fused with a cell in G 1, the G 1 cell immediately began mitosis—a spindle formed and chromatin condensed, even though the chromosome had not been duplicated. Regulation of cell cycle

LE G 1 checkpoint G1G1 S M M checkpoint G 2 checkpoint G2G2 Control system

LE G1G1 G 1 checkpoint G1G1 G0G0 If a cell receives a go-ahead signal at the G 1 checkpoint, the cell continues on in the cell cycle. If a cell does not receive a go-ahead signal at the G 1 checkpoint, the cell exits the cell cycle and goes into G 0, a nondividing state.

Fig a Time (a) Fluctuation of MPF activity and cyclin concentration during the cell cycle Cyclin concentration MPF activity M M M SS G1G1 G1G1 G1G1 G2G2 G2G2

Fig b Cyclin is degraded Cdk MPF Cdk M S G1G1 G 2 checkpoint Degraded cyclin Cyclin (b) Molecular mechanisms that help regulate the cell cycle G2G2 Cyclin accumulation

Cells in phase G 1 fluoresce bright red. As they transition into the S phase and begin DNA replication, Cdt1 levels are dramatically reduced while Geminin levels increase. This results in faint yellow fluorescence early in G 1 /S that soon gives way to robust green fluorescence, (G 2 ) which lasts until the cell re-enters G 1 phase. The Fucci cell cycle visualization method. Sakaue-Sawano, A.,et al. Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell 132, 487–498 (2008).

Fig Petri plate Scalpels Cultured fibroblasts Without PDGF cells fail to divide With PDGF cells prolifer- ate 10 µm Experimental set-up for cell growth

LE Cell cycle-stimulating pathway Growth factor G protein Receptor MUTATION Protein kinases (phosphorylation cascade) NUCLEUS Hyperactive Ras protein (product of oncogene issues signals on its own. Transcription factor (activator) DNA Gene expression Protein that stimulates the cell cycle Signal transduction pathway for cell cycle stimulation

Fig Anchorage dependence Density-dependent inhibition (a) Normal mammalian cells (b) Cancer cells 25 µm Cancer tissue lacks growth inhibition (or may have internal over stimulation (Ras mutations)

Science 26 January 2007: Vol no. 5811, pp DOI: /science Asymmetric Inheritance of Mother Versus Daughter Centrosome in Stem Cell Division

Asymmetric segregation is produced by centrosomes Fig. 1. GFP-labeled daughter centrosomes migrate away from the niche. Stereotyped positioning of centrosomes in male germline stem-cells during interphase sets up the orientation of the mitotic spindle [adapted from (6)]. Red, centrosome; blue, hub; green, tubulin. Drosophila male germline stem cells (GSCs) are maintained through attachment to somatic hub cells, which constitute the stem cell niche. Hub cells secrete the signaling ligand Upd, which activates the Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway in the neighboring germ cells to specify stem cell identity (4, 5). Drosophila male GSCs normally divide asymmetrically, producing one stem cell, which remains attached to the hub, and one gonialblast, which initiates differentiation. This stereotyped asymmetric outcome is controlled by the orientation of the mitotic spindle in GSCs: The spindle lies perpendicular to the hub so that one daughter cell inherits the attachment to the hub, whereas the other is displaced away (6).456

Science 26 January 2007: Vol no. 5811, pp DOI: /science Centrosome positions are controlled by cell junctions Fig. 3. Centrosomes next to the hub harbor robust microtubule arrays. Electron micrograph and summary diagram of a proximal centrosome in a GSC. Arrowheads in (A') show a microtubule that runs from the centrosome to the adherens junction.

Science 26 January 2007: Vol no. 5811, pp DOI: /science Centrosomin is a protein that controls centrosome segregation Fig. 4. Mutant for centrosomin (cnn) ; cnn is required for nonrandom segregation of mother and daughter centrosomes. Centrosomin (cnn) is an integral centrosomal protein required to anchor astral microtubules to centrosomes

Model for JAK pathway activity in embryogenesis. Upd is the ligand for stimulation of the JAK pathway. Upd protein is produced in hub cells, in which it is glycosylated and secreted, and diffusion is restricted by association with the ECM. Through binding of Upd to a yet unidentified receptor, the Hop JAK is stimulated, resulting in phosphorylation of Stat92E. Ultimately, transcription of specific genes, such as eve, is activated. D. A. Harrison, P. E. McCoon, R. Binari, M. Gilman, N. Perrimon, Genes Dev. 12, 3252 (1998) Hub cells control stem cell renewal and differentiation