leicester warwick medical school cellular adaptations dr gerald saldanha department of pathology...
TRANSCRIPT
![Page 1: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/1.jpg)
Leicester Warwick Medical School
Cellular Adaptations
Dr Gerald SaldanhaDepartment of Pathology
Email: [email protected]
![Page 2: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/2.jpg)
Introduction
• This presentation will ….– Focus on adaptive responses in cell growth
& differentiation– Describe cell signalling pathways– Introduce the cell cycle
![Page 3: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/3.jpg)
Control of cell growth
• Cells in a multicellular organism communicate through chemical signals
• Hormones act over a long range• Local mediators are secreted into the
local environment• Some cells communicate through direct
cell-cell contact
![Page 4: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/4.jpg)
![Page 5: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/5.jpg)
Control of cell growth
• Cells are stimulated when extra cellular signalling molecules bind to a receptor
• Each receptor recognises a specific protein (ligand)
• Receptors act as transducers that convert the signal from one physical form to another.
![Page 6: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/6.jpg)
Signalling molecules
• Most signalling molecules cannot pass through the cell membrane– Their receptors are in the cell
membrane
• Small hydrophobic signal molecules can diffuse directly into the cell cytoplasm– Their receptors are cytoplasmic
or nuclear
![Page 7: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/7.jpg)
Signalling molecules
• Hormones– Insulin, – Cortisol– etc
• Local mediators– Epidermal Growth Factor (EGF), – Platelet Derived Growth Factor (PDGF)– Fibroblast Growth Factor (FGF)– TGF– Cytokines, e.g. Interferons, Tumour necrosis factor (TNF)
![Page 8: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/8.jpg)
Receptors
• There are three main classes of receptors….
• Ion-channel-linked receptors
• G-protein-linked receptors
• Enzyme-linked receptors
![Page 9: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/9.jpg)
Receptors
• Ion channel-linked receptors are important in neural signalling
• G-protein and enzyme linked receptors respond by activating cascades of intracellular signals
• These signals alter the behaviour of the cell
![Page 10: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/10.jpg)
G-protein-linked receptors
• G-protein-linked receptors activate a class of GTP-binding proteins (G-proteins)
• G proteins are molecular switches
• They are turned on for brief periods while bound to GTP
• They switch themselves off by hydrolysing GTP to GDP
![Page 11: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/11.jpg)
![Page 12: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/12.jpg)
G proteins
• Some G proteins directly regulate ion channels
• Others activate adenylate cyclase, thus increasing intracellular cyclic AMP
• Some activate the enzyme Phospholipase C, thus increasing intracellular inositol triphosphate (IP3) and Diacylglycerol (DAG)
![Page 13: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/13.jpg)
![Page 14: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/14.jpg)
Enzyme-linked receptors
• Many receptors have intracellular domains with enzyme function
• Most are receptor tyrosine-kinases• They phosphorylate tyrosine residues in
selected intracellular proteins• These receptors are activated by
growth factors, thus being important in cell proliferation
![Page 15: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/15.jpg)
![Page 16: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/16.jpg)
Receptor tyrosine kinases
• Receptor tyrosine kinase activation results in assembly of an intracellular signalling complex
• This complex activates a small GTP-binding protein, Ras
• Ras activates a cascade of protein kinases that relay the signal to the nucleus
• Mutations that make Ras hyperactive are a common way of inducing increased proliferation in cancer
![Page 17: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/17.jpg)
![Page 18: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/18.jpg)
Signalling: cytoplasm to nucleus
• Many signalling cascades culminate in activation of nuclear transcription factors
• Transcription factors alter gene expression
• C-jun and c-fos ( that form an AP1 complex) and c-myc are three important transcription factors
![Page 19: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/19.jpg)
Signalling pathway interactions
• There are many signalling molecules and receptors
• A given cell expresses only a subset of receptors
• Different intracellular signalling pathways interact
• This enables cells to respond appropriately to complex combinations of signals
![Page 20: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/20.jpg)
![Page 21: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/21.jpg)
![Page 22: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/22.jpg)
Cell signalling and proliferation
• Animal cells proliferate when stimulated by growth factors
• These bind mainly to receptor tyrosine kinases• These signalling pathways override the normal
brakes on proliferation• These brakes are part of the cell cycle control
system• This ensures that cells divide only under
appropriate circumstances
![Page 23: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/23.jpg)
The cell cycle
• The eukaryotic cell cycle consists of distinct phases
• The most dramatic events are nuclear division (mitosis) and cytoplasmic division (cytokinesis)
• This is the M phase• The rest of the cell cycle is called
interphase which is, deceptively, uneventful
• During interphase the cell replicates its DNA, transcribes genes, synthesises proteins and grows in mass
![Page 24: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/24.jpg)
Phases of the cell cycle
• S phase – DNA replicates• M phase – nucleus divides
(mitosis) and cytoplasm divides (cytokinesis)
• G1 phase – gap between M and S phase
• G2 phase – between S and M phase
![Page 25: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/25.jpg)
Cell cycle control
• Cell cycle machinery is subordinate to a cell cycle control system
• The control system consists mainly of protein complexes
• These complexes consist of a cyclin subunit and a Cdk subunit
• The cyclin has regulatory function, the Cdk catalytic function
![Page 26: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/26.jpg)
Cell cycle control
• Cdk expression is constant, but cyclin concentrations rise and fall at specific times in the cell cycle
• The Cdks are cyclically activated by cyclin binding and by phosphorylation status
• Once activated, Cdks phosphorylate key proteins in the cell
![Page 27: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/27.jpg)
![Page 28: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/28.jpg)
Cell cycle control
• Different cyclin-Cdk complexes trigger different cell cycle steps
• Some drive the cell into M phase, others into S phase
• The cell cycle control system has in-built molecular breaks (checkpoints)
• The checkpoints ensure that the next step does not begin until the previous one is complete
![Page 29: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/29.jpg)
![Page 30: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/30.jpg)
The G1 checkpoint
• The G1 checkpoint has been widely studied
• The retinoblastoma (Rb) protein plays a key role at this checkpoint
• The Rb protein function is determined by its phosphorylation status
• S phase cyclin-Cdk complexes phosphorylate Rb
![Page 31: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/31.jpg)
![Page 32: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/32.jpg)
The G1 checkpoint
• This checkpoint is influenced by the action of cyclin-dependant kinase inhibitors (CKIs, e.g. p21, p16)
• E.g. p53 senses DNA damage and induces p21 expression
• CKIs inactivate cyclin-Cdk complexes
![Page 33: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/33.jpg)
![Page 34: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/34.jpg)
Cellular adaptations of growth and differentiation
• Cells must respond to a variety of stimuli that may be hormonal, paracrine or through direct cell contact
• These stimuli may arise under physiological or pathological conditions
• The way that cells adapt in terms of growth and differentiation depends in part on their ability to divide
![Page 35: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/35.jpg)
Cellular proliferative capacity
• Tissues can be classified according to the ability of their cells to divide
• Some tissues contain a pool of cells that move rapidly from one cell cycle to the next. These are labile cells
![Page 36: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/36.jpg)
Cellular proliferative capacity
• Some cells dismantle their cell cycle control machinery and exit the cell cycle
• These cells are said to be in G0.
• Some of these cells can re-enter the cell cycle when stimulated, e.g. by growth factors. These are stable cells
• Others are unable to re-enter the cell cycle. These are permanent cells
![Page 37: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/37.jpg)
Growth and differentiation responses
• Hyperplasia
• Hypertrophy
• Atrophy
• Metaplasia
![Page 38: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/38.jpg)
Hyperplasia
• Increase in the number of cells in an organ or tissue, which may then have an increased size
![Page 39: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/39.jpg)
Hyperplasia: causes
• Hyperplasia can only occur in tissues containing labile or stable cells
• Hyperplasia may occur under pathological or physiological conditions
![Page 40: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/40.jpg)
Physiological Hyperplasia
• Hormonal e.g. endometrium
• Compensatory, e.g. partial hepatectomy– TGF alpha, HGF– TGF beta
![Page 41: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/41.jpg)
Pathological hyperplasia
• Excessive hormone/growth factor stimulation
• Often occurs alongside hypertrophy
• Associated with increased risk for cancer
• E.g. Prostate, endometrium
![Page 42: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/42.jpg)
![Page 43: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/43.jpg)
![Page 44: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/44.jpg)
![Page 45: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/45.jpg)
![Page 46: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/46.jpg)
Hypertrophy
• An increase in cell size, and resultant increase in organ size
![Page 47: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/47.jpg)
Hypertrophy: causes
• Occurs in permanent cells
• Due to synthesis of more cellular structural components
• Physiological or pathological causes
![Page 48: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/48.jpg)
Physiological hypertrophy
• Increased functional demand, e.g. skeletal muscle– Mechanical
• Hormonal, e.g. Uterus in pregnancy– Usually a combination of hypertrophy and
hyperplasia
![Page 49: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/49.jpg)
Pathological hypertrophy
• Increased functional demand e.g. cardiac muscle– Hypertension – valvular heart disease
![Page 50: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/50.jpg)
![Page 51: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/51.jpg)
![Page 52: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/52.jpg)
Atrophy
• Shrinkage in cell size by loss of cell substance
– Term is often used loosely to describe reduced organ size that may be related to cell loss rather than shrinkage
![Page 53: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/53.jpg)
Atrophy: causes
• Reduced workload
• Loss of innervation
• Reduced blood supply
• Inadequate nutrition
• Loss of endocrine stimulation
• Ageing
![Page 54: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/54.jpg)
![Page 55: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/55.jpg)
![Page 56: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/56.jpg)
![Page 57: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/57.jpg)
Metaplasia
• Reversible change of one adult cell type to another adult cell type
![Page 58: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/58.jpg)
Metaplasia: causes
• An adaptive response to various stimuli• New cell type is better adapted to
exposure to the stimulus• The stimulus that induced metaplasia
may, later, induce cancer, e.g. squamous cell carcinoma of the bronchus
• Metaplasia in mesenchymal tissues is often less clearly adaptive
![Page 59: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/59.jpg)
![Page 60: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/60.jpg)
![Page 61: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/61.jpg)
Hypoplasia
• Incomplete development of an organ with reduced cell numbers
![Page 63: Leicester Warwick Medical School Cellular Adaptations Dr Gerald Saldanha Department of Pathology Email: gss4@le.ac.uk](https://reader035.vdocuments.us/reader035/viewer/2022081512/551ba21f550346942b8b5890/html5/thumbnails/63.jpg)
Summary
• Cells communicate through signalling pathways
• Signalling pathways influence the cell cycle control system
• This determines a cells ability to divide• A cells replicative capacity influences its
adaptive responses to changes in the tissue environment