human dev revision

Cell theory:

all living things are made of cells

cell = basic unit of life

all cells come from pre-existing cells

cells contain hereditary info (DNA)

cells share similar chemical makeup

cell function depends on subcellular structures/organelle activity

Why multicellular?

↑ surface area for nutrient/gas exchange + waste removal

specialization = different cells do different jobs

Major organelles + function

Nucleus:

contains DNA

nuclear envelope + pores regulate transport

nucleolus = ribosome assembly

Mitochondria

ATP production/cellular respiration

roles in cell cycle, differentiation, apoptosis

have own DNA; maternally inherited

Rough ER

ribosome-studded

synthesis/processing of proteins for secretion/membranes

Smooth ER

lipid synthesis

detoxification

carbohydrate metabolism

Golgi apparatus

modifies, sorts, packages proteins/lipids

Lysosomes

digestive enzymes; breakdown/recycling; can contribute to apoptosis

Peroxisomes

fatty acid metabolism + detoxification

Vacuoles/vesicles

storage/transport

Ribosomes

protein synthesis

Cilia

move substances across cell surface

Flagella

whole-cell movement, eg sperm

DNA + chromosomes

DNA = deoxyribonucleic acid

double helix of nucleotides: A, T, C, G

sequence of bases forms genes + regulatory regions

humans: 23 pairs of chromosomes = 22 autosome pairs + 1 sex chromosome pair

DNA wraps around histones for packaging

DNA + histones = chromatin

Chromatid = one half of a replicated chromosome

Gene structure

Gene = DNA sequence producing a functional product (usually protein, sometimes functional RNA)

Promoter: near 5’ end; binds transcription factors + RNA polymerase; starts transcription

Coding region: part containing exons

Exons: retained in mature mRNA; code for protein

Introns: removed during splicing; non-coding; can contain

regulatory elements

Enhancer: increases transcription when TFs bind

Silencer/repressor region: decreases transcription

3’ UTR: non-coding tail region; helps transcript processing, stability, termination, translation control

Central dogma

DNA → RNA → Protein

1. Transcription

in nucleus

DNA copied into pre-mRNA / nuclear RNA

2. RNA processing

5’ cap added

poly-A tail added

introns removed by splicing

exons joined

makes mature mRNA

3. Translation

mRNA exits nucleus to cytoplasm

ribosome binds 5’ end

starts at start codon (AUG)

reads mRNA in codons (3 bases each)

each codon codes for 1 amino acid

stops at stop codon

polypeptide folds/modifies into functional protein

Important gene expression ideas

One gene can make multiple proteins via alternative splicing

different exon combinations → different mRNAs → different protein isoforms

some genes make functional RNAs only, eg miRNA

antisense/complementary RNA can bind mRNA and block translation

Regulation of gene expression can happen at multiple levels:

1. Chromatin accessibility

DNA wrapped around histones forms nucleosomes

Euchromatin = loose/open = transcriptionally active

Heterochromatin = tight/condensed = inactive

Histone acetylation usually opens chromatin → ↑ transcription

Histone methylation can activate or repress depending on site

this is part of epigenetic regulation = changes in expression without changing DNA sequence

2. DNA methylation

methyl added at CpG sites (CH3)

usually represses transcription, especially at promoters/enhancers

important in genomic imprinting

can be inherited through cell division

3. Transcriptional regulation

Transcription factors (TFs) bind specific DNA sequences

TFs can:

activate transcription

repress transcription

recruit chromatin modifiers

link enhancers to promoters by DNA looping

gene expression depends on combination + ratio of activators/repressors

different tissues express different TFs → cell-type specific gene expression

4. RNA-level regulation

Alternative splicing changes protein produced

miRNAs bind target mRNA via RISC

degrade mRNA or block translation

bad splicing can produce non-functional proteins

5. Translation regulation

mRNA can be prevented from being translated

antisense RNAs/miRNAs can reduce protein output even if mRNA exists

6. Post-translational modification

protein changed after translation

examples:

phosphorylation

methylation

acetylation

changes activity, localisation, stability, interactions

Predicting effects of regulation

More open chromatin / more histone acetylation → ↑ transcription

More promoter DNA methylation → ↓ transcription

Activator TF binds enhancer → ↑ gene expression

Repressor binds silencer/promoter → ↓ gene expression

Alternative splicing changes exon use → different protein made

miRNA added → ↓ mRNA stability or ↓ translation

post-translational modification → protein function changes without changing mRNA level

Cytoskeleton

Three main parts:

1. Microtubules

largest

made of α- and β-tubulin

roles:

cell shape

intracellular transport

mitotic spindle/cell division

cilia + flagella structure

2. Microfilaments (actin filaments)

made of actin

roles:

cell shape changes

muscle contraction

cell crawling/migration

cytokinesis

3. Intermediate filaments

strongest tension-bearing support

structural stability

cell-type specific, eg keratin in epithelial cells

Cytoskeleton in movement

cytoskeleton is essential for:

maintaining shape

polarity

movement of organelles

cell migration

cell movement responds to external signals

important in development, tissue repair, immune cell movement

examples: neural crest cells and primordial germ cells migrate during development

Development + gene regulation

all cells start with same DNA but become different because they express different genes

changes in transcription factors + proteins over generations of cells drive cell differentiation

master TFs control many downstream genes/other TFs

eg Oct4, Sox2, KLF4

gene control often uses:

positive feedback = reinforces own expression/cell identity

negative feedback = limits expression

groups of interacting genes/TFs = gene regulatory networks (GRNs)

Environment can affect gene expression

nutrition, drugs, pathogens, toxins can alter gene expression

mechanisms:

epigenetic changes

DNA damage/mutation

altered transcription factor activity

Ultra-mini memory lines

Open chromatin = ON

Closed chromatin = OFF

Promoter starts

Enhancer boosts

Silencer suppresses

Exons stay, introns go

DNA → RNA → protein

One gene can make many proteins

miRNA usually lowers expression

Cytoskeleton = shape + transport + movement

WEEK 2

Cells in the body share a common genome but become different because they express different genes. Cell-specific phenotype/function depends on which genes are ON vs OFF, controlled by intrinsic + extrinsic signals.

1. Common genome

Most body cells have the same DNA/genome

Different cell types do not usually have different genomes — they have different gene expression

Proven by nuclear transplantation/cloning

Gurdon (frog): adult skin-cell nucleus of a frog could produce a whole frog

Dolly the sheep: mammalian proof of same idea

2. Why cells become different

Different cells = different patterns of gene expression

Some genes are housekeeping genes → expressed in almost all cells

eg metabolism, protein synthesis

Other genes are cell-specific

eg neuron genes, epithelial genes

This selective gene activation/inactivation drives differentiation + specialisation

3. Intrinsic vs extrinsic influences

Intrinsic = inside cell

transcription factors

chromatin state

gene regulatory networks

existing proteins/RNAs in cell

Extrinsic = outside cell

environment: temperature, oxygen

growth factors

morphogens

cytokines

hormones

small signaling molecules

4. Plasma membrane in signaling

Cell membrane helps cell respond to outside cues:

survive

grow + divide

differentiate

die (apoptosis)

A single extracellular signal binds a receptor → intracellular signaling cascade → changes in:

metabolism

gene expression

cytoskeleton / movement / shape

5. Differentiation potential

Totipotent = can form all cell types incl extraembryonic tissues

Pluripotent = can form all body cell types

Multipotent = can form several related cell types

Nullipotent / terminally differentiated = highly specialized, little/no further differentiation potential

6. Transcription factors

Proteins that regulate gene expression by binding regulatory DNA, especially promoters

Gene activation needs the right TFs

in the right cell

at the right time

in the right place (usually nucleus)

Some TFs are widespread, others are cell-type specific

7. Master regulators

Certain TFs act as master regulators

They switch on cascades of other genes/TFs

Example:

SRY on Y chromosome → activates testis-development pathway

eyeless in Drosophila → activates eye-development program

8. Big idea

Same genome + different regulation = different cell types

9. Tiny exam lines

Cells share same genome; differ by gene expression

Intrinsic + extrinsic cues control cell fate

TFs regulate promoter activity

Master TFs trigger cascades

Differentiation = progressive specialization

Human development can be studied in other organisms because many developmental processes and genes are evolutionarily conserved.

1. Evolution basics

All organisms are related by descent from a common ancestor

Evolution = change in heritable traits across generations

Produces biodiversity and new species

2. Natural selection

Traits that improve survival/reproduction become more common

Acts on existing variation in populations

Driven by environment

Example: Darwin’s finches with different beaks

3. Artificial selection

Human-directed selection / selective breeding

Example:

wolves → dogs

teosinte → corn

4. Sources of variation

Mutation

Meiosis / crossing over

Sexual reproduction / independent assortment

5. Homology

Homologous structures = structures similar in position, structure, and evolutionary origin, but not always function

Example: vertebrate forelimbs

bird wing

bat wing

whale flipper

cat/horse/human forelimb

6. Embryos reflect shared ancestry

Early embryos of vertebrates look similar

Shared features like tails and pharyngeal/gill slit regions

Shows developmental conservation across species

7. DNA + orthologous genes

Genomes of different species retain similarity

Orthologous genes = genes in different species descended from common ancestral gene, often with similar function

More similar DNA = more closely related species

Developmental genes are often highly conserved

Example: Hox genes are conserved body-plan regulators across animals

8. Why model organisms work

Human development can be modelled because many basic cellular/developmental mechanisms are conserved

Direct human experimentation is limited/ethical issues

Different models suit different questions

Model organisms cheat sheet

Bacteria / yeast

Best for: basic cell biology, metabolism, mitosis/meiosis
Pros: simple, cheap, fast
Cons: too far from humans for complex development

C. elegans

Best for: cell lineage, apoptosis, nervous system development
Pros: tiny and easy to grow

fast life cycle (~3 days egg → adult)

fate mapping possible

adult has fixed 959 somatic cells

~40% of human disease genes have orthologs
Cons: simple invertebrate, limited for complex vertebrate systems

Drosophila melanogaster

Best for: genetics, embryonic patterning, developmental gene.

Pros:

cheap

fast breeding

short generations

simple genetics

~75% human disease genes have orthologs / many disease genes shared

Cons:

invertebrate

lacks vertebrate features like blood vessels; lecture notes also mention limited immune-system comparability

Zebrafish

Best for: vertebrate development, live imaging, organ development

Pros:

external fertilisation/development

transparent embryos

rapid development

easy mutation studies

~70% human genes have counterparts

Cons: still not mammal; some human-specific processes not modelled as well

Xenopus (frog)

Best for: reproductive biology, oocytes, early development, cloning history
Pros:

large eggs/oocytes

useful for nuclear transplantation studies

simpler nervous system useful for neurodevelopment
Cons: less directly human-like than mammal models

Chick

Best for: embryology, body patterning, accessible embryo observation
Pros:

embryo easy to observe via windowing

similar broad embryonic stages to humans

historically important
Cons: not mammalian; some physiology differs

Mouse

Best for: mammalian development, disease models, gene manipulation
Pros:

closest commonly used model here to humans

lots of mutant/knockout lines

good for human-like disease studies
Cons:

ethical issues

slower/more expensive

embryo less easy to observe/manipulate live than fish/chick

Sheep / larger mammals

Best for: fetal physiology, lung development, large-animal studies
Pros: more human-like physiology in some systems
Cons: expensive, harder to maintain, bigger ethical/logistical issues

How to choose the right model

Ask:

What process am I studying?

Do I need simple genetics or human-like physiology?

Do I need live imaging?

Do I need fast generations?

Do I need a vertebrate or a mammal?

Ultra-crammed memory lines

Lecture 3

Same genome, different expression

Differentiation = selective gene expression

Intrinsic + extrinsic cues control fate

TFs bind promoters

Master regulators start gene cascades

Lecture 4

Evolution = heritable change over generations

Natural selection favours useful traits

Homologous = same origin, maybe diff function

Orthologous genes = related genes across species

Model organisms work because development is conserved

Week 3

1. Big picture

Fertilisation = sperm + egg unite → zygote

Zygote = diploid + totipotent

Early embryo then undergoes:

cleavage

blastocyst formation

implantation

gastrulation

body axis patterning

2. Gamete production

Meiosis

Produces haploid gametes

Fusion of haploid sperm + haploid egg restores diploid chromosome number in zygote

Spermatogenesis

Starts at puberty

Continues through life

1 spermatocyte → 4 haploid spermatids / sperm

Sperm carry X or Y chromosome

Oogenesis

Begins during embryonic life

arrest/Pause in prophase I

Resumes at puberty

Usually 1 oocyte ovulated/cycle

Arrests again at metaphase II

Meiosis only fully completes if fertilisation occurs

1 oocyte → 1 functional ovum + 3 polar bodies

Egg always carries X chromosome

Key comparison

Male: 4 functional gametes

Female: 1 functional gamete

Oogenesis is asymmetric to preserve cytoplasm/nutrients in egg

Fertility point

Female fertility more affected by age because oocytes are formed early and remain arrested for years

3. Fertilisation basics

Usually occurs in the fallopian tube / oviduct, near the ovary

Sperm must be present around ovulation

Sperm can survive about 5–6 days

Fertilisation produces a zygote

Many gametes/zygotes are chromosomally abnormal:

oocytes: 20–37%

sperm: 7–15%

zygotes: up to 40%

Major chromosomal abnormalities often cause early miscarriage / failed development

4. Differentiation potential

Totipotent: can form embryo + extraembryonic tissues

Pluripotent: can form many body cell types, but not all extraembryonic tissues

As development continues, cells become:

multipotent

then more restricted

then terminally differentiated

Important examples

Zygote = totipotent

Inner cell mass = pluripotent

5. Cleavage and preimplantation development

Cleavage

Rapid mitotic divisions after fertilisation

Occurs over first 3–4 days

Cell number increases, but embryo overall stays within zona pellucida early on

By day 5: blastocyst

About ~100 cells

Main parts:

trophoblast = outer layer

inner cell mass (ICM) = forms embryo proper

zona pellucida still around embryo until hatching

Hatching

Blastocyst must hatch from zona pellucida

Needed so it can interact with uterus and implant

6. Implantation

Occurs around day 6–9

Blastocyst implants into uterine wall / endometrium

If embryo implants in wrong place, eg fallopian tube → ectopic pregnancy (dangerous)

7. Inner cell mass changes

Delamination

Around day 6–8, inner cell mass separates into:

Epiblast: forms the embryo

Hypoblast: contributes to extraembryonic tissues

Epiblast = embryo-forming layer

Hypoblast = extraembryonic support role

8. Gastrulation

Gastrulation converts embryo into three germ layers

Germ layers:

ectoderm

mesoderm

endoderm

Importance

Major step in turning simple embryo into organised body plan

Cells become less potent and more specialised during this process

Memory line:

Gastrulation = formation of 3 germ layers

9. Germ layers

Ectoderm → skin + nervous system broadly

Mesoderm → muscle, bone, blood, connective tissues broadly

Endoderm → gut lining + many internal organ linings broadly

For this lecture, main thing is to know:

there are 3 germ layers

gastrulation forms them

10. Mitosis + cell cycle

Cell cycle

G1 = growth

S = DNA replication

G2 = preparation for division

M phase = mitosis

Some cells enter G0 = quiescent / non-dividing state

Checkpoints

G1/S checkpoint

G2/M checkpoint

Check DNA integrity and readiness to divide

If damage severe → cell cycle arrest or apoptosis

Cyclins + CDKs

Control progression through cell cycle

Cyclins rise/fall during cycle

CDKs activated by cyclins

Example:

Cyclin D + CDK4 helps drive G1 → S

Cyclin E + CDK2 helps prepare for DNA synthesis

11. Mitosis stages

Prophase: chromatin condenses, spindle begins forming

Metaphase: chromosomes line up at metaphase plate

Anaphase: sister chromatids separate to opposite poles

Telophase: nuclei reform, chromosomes decondense

Cytokinesis: cytoplasm divides → 2 daughter cells

Important point

Actin microfilaments help cytokinesis by forming cleavage furrow

12. Why mitosis matters here

Early embryo grows from one cell to many cells by mitosis

Also essential throughout life for:

growth

tissue repair

cell replacement

13. Karyotyping

Best done at metaphase

Chromosomes are condensed and clearly visible

Used to detect:

abnormal chromosome number

structural chromosome abnormalities

aneuploidy

14. Embryonic axes

Need to know the embryo starts getting organised along body axes:

anterior–posterior

dorsal–ventral

left–right

15. Node and left-right asymmetry

Node

Special embryonic structure important for breaking symmetry

Helps establish left vs right side of embryo

Monocilia

Present on node cells

Generate leftward nodal flow of extraembryonic fluid

Why nodal flow matters

This leftward flow directs signalling molecules preferentially to the left side

Helps activate left-sided developmental program

16. Signals involved in left-right patterning

Node-associated signals mentioned:

Sonic hedgehog (Shh)

FGF8

also nodal

lefty

other pathways also involved, eg:

BMPs

Wnts

Outcome

These signals activate gene cascades that drive asymmetrical development of organs مثل:

heart looping

gut looping

liver/spleen positioning

17. Left-right dynein

Left-right dynein is important in monocilia function

Highly conserved across species

Needed for proper cilia-driven nodal flow

If cilia do not work properly, left-right patterning can fail

18. Situs inversus / Kartagener syndrome

Disorder linked to defective dynein / immotile cilia

Approx. 1 in 10,000

Can cause situs inversus = organ positions reversed

In about 50% of affected cases, complete inversion occurs

Organs may still function normally despite reversed placement

Mechanism

Cilia fail to move signalling factors leftward

Signals disperse more randomly

Organ placement becomes randomised/reversed rather than normal left-right patterning

Important clarification

This does not cause doubling of organs like “two hearts”

One side still ends up dominant

19. Absolute must-know definitions

Zygote: fertilised egg; diploid; totipotent

Cleavage: rapid early mitotic divisions

Blastocyst: day ~5 embryo with trophoblast + ICM

Implantation: attachment into uterus

Delamination: ICM splits into epiblast + hypoblast

Gastrulation: formation of ectoderm, mesoderm, endoderm

Node: breaks symmetry; starts left-right patterning

Nodal flow: leftward fluid flow created by monocilia

Situs inversus: reversed organ placement

20. Ultra-crammed exam lines

Fertilisation in fallopian tube → diploid totipotent zygote

Zygote = totipotent; ICM = pluripotent

Cleavage → blastocyst by day 5

Blastocyst = trophoblast + inner cell mass

Implantation ≈ day 6–9

Epiblast forms embryo; hypoblast forms extraembryonic tissues

Gastrulation forms ectoderm, mesoderm, endoderm

Mitosis stages: P M A T + cytokinesis

Cyclins + CDKs regulate cell cycle

Node + monocilia create leftward nodal flow

Shh/FGF8/nodal-lefty help establish left-right asymmetry

Defective cilia/dynein → situs inversus

Week 4.

1. Cell communication: why it matters

Cells communicate to control:

survival

proliferation

differentiation

migration

shape/metabolism changes

apoptosis

Key principle: the same signal can cause different effects in different cells depending on:

receptor present

intracellular proteins present

developmental stage/context

2. Signal transduction: how a signal affects the nucleus

General pathway

Signal produced

Signal binds receptor

Intracellular signalling pathway activated

Signal reaches nucleus

Gene expression changes

Cell behaviour changes

Key points

No receptor = no response

Hydrophilic signals usually bind cell-surface receptors

Lipid-soluble/small signals can cross membrane and bind intracellular receptors

Fast responses: no major gene expression change

Slow responses: involve transcription/protein synthesis

3. Four major types of cell-cell signalling

A. Contact-dependent / juxtacrine

requires direct cell-cell contact

very local

important for precise patterning

B. Paracrine

signal released locally

acts on nearby cells

short-range diffusion

often forms gradients

major developmental families:

TGF-β/BMP

C. Synaptic

neuron releases neurotransmitter across synapse

very fast

highly specific target

D. Endocrine

hormones travel in bloodstream

act over long distances

target cell must have receptor

Extra: Autocrine

cell signals to itself

4. Morphogens and morphogen gradients

Morphogen: A signalling molecule that forms a concentration gradient and causes different cell fates at different concentrations.

Morphogen gradient: produced from a localised source,

diffuses away

highest concentration near source, lower further away

French flag model

high concentration → one fate

medium → another fate

low → another fate

Why morphogens matter

They provide positional information:

tell cells where they are

help pattern tissues

control differentiation and organ formation

Gradient control

Gradients are shaped by:

enzymatic degradation

ECM binding

antagonists

receptor uptake/internalisation

5. Why cells die

In development

sculpt tissues

separate digits

form hollow/lumen structures

control cell number

In tissue homeostasis

remove old cells

replace high-turnover cells

remove damaged/infected cells

In disease

DNA damage

toxins

infection

hypoxia

nutrient deprivation

loss of survival factors

6. Apoptosis

Programmed, regulated cell death

Importance

development

homeostasis

removal of damaged/mutated cells

Triggers

Extracellular:

death signals

withdrawal of survival factors

immune signals

hypoxia

toxins

nutrient deprivation

Intracellular:

DNA damage

severe stress

abnormal Ca²⁺

Main steps

Cell shrinkage

Caspase activation

Cytoskeleton breakdown

Pyknosis = chromatin condensation

Karyorrhexis = nuclear/DNA fragmentation

Membrane blebbing

Apoptotic bodies form

Phagocytosis

Key feature

Contents stay membrane-bound, so little/no inflammation

7. Necrosis

Uncontrolled, unregulated cell death

Causes

trauma

infection

toxins

hypoxia

severe injury

Features

cell swelling

membrane rupture

contents spill out

inflammation

damages nearby tissue

8. Apoptosis vs necrosis

Apoptosis

regulated

cell shrinks

membrane stays intact

ordered fragmentation

no major inflammation

minimal surrounding damage

Necrosis

unregulated

cell swells

membrane ruptures

contents leak out

inflammation common

surrounding tissue damaged

ECM + connective tissue

9. Extracellular matrix (ECM)

Collection of proteins and molecules outside cells that support and organise tissues.

Main components

fibrous proteins

collagen

elastic fibres

reticular fibres

GAGs

eg hyaluronan

proteoglycans

glycoproteins

fibronectin

laminin

Functions

Mechanical:

support

tensile strength

elasticity

barrier

scaffold

Non-mechanical:

regulates migration

affects survival/proliferation/differentiation

stores/presents signalling molecules

Important idea

ECM is dynamic, not just filler space

10. Connective tissue

Definition

Tissue with cells embedded in abundant ECM

Key features

cells more widely spaced

lots of ECM

often vascular

support/binding/protection/transport roles

Made of

Cells:

fibroblasts

chondrocytes

osteocytes

macrophages/leukocytes

adipocytes

Fibres:

collagen

elastic

reticular

Ground substance:

proteoglycans

GAGs

glycoproteins

tissue fluid

11. Classification of connective tissue

Loose connective tissue

loose fibres/cells

more ground substance

flexible

well vascularised

Dense regular CT

parallel collagen

strength in one direction

eg tendons, ligaments

Dense irregular CT

collagen in many directions

resists stress from many angles

eg dermis

Other specialised CT

blood

cartilage

bone

Junctions

12. Six cellular junctions

1. Tight junctions

barrier between cells

prevent leakage between cells

maintain apical-basal polarity

2. Adherens junctions

cell-cell anchoring

cadherins

linked to actin

maintain cohesion/shape

3. Desmosomes

strong cell-cell adhesion

resist mechanical stress

linked to intermediate filaments

use desmosomal cadherins

4. Gap junctions

direct communication channels

allow ions/small molecules through

made of connexons/connexins

5. Focal adhesions

cell-ECM attachment

integrins

link ECM to actin

important in migration/signalling

6. Hemidesmosomes

anchor epithelial cells to basal lamina

integrins

link to intermediate filaments

bind laminin externally

Epithelia vs mesenchyme

13. Epithelial tissue

tightly packed cells

sheet-like

little ECM

polarised

usually non-motile

sits on basement membrane

many junctions

14. Mesenchymal tissue

loosely associated cells

lots of ECM

non-polarised

motile/migratory

fewer stable junctions

15. EMT and MET

EMT = epithelial → mesenchymal transition

lose adhesion

gain motility

migrate

important in gastrulation and neural crest migration

MET = mesenchymal → epithelial transition

cells become more adhesive

form organised sheets again

Epithelia

16. Functions of epithelia

protection

absorption

secretion

transport

sensation

17. Five major epithelial characteristics

Tightly packed cells

Polarity (apical + basal surfaces)

Basement membrane support

Avascular

Rapid regeneration

Also:

strong junctions

form sheets

usually innervated

18. Classification of epithelia

By shape

squamous = flat

cuboidal = cube-like

columnar = tall

By layers

simple = one layer

stratified = many layers

pseudostratified = looks multilayered but all touch basal lamina

transitional = stretches

By specialisations

microvilli = ↑ surface area

cilia = move substances

goblet cells = mucus secretion

keratinisation = protection

19. Basement membrane / basal lamina

Basal lamina

Thin specialised ECM under epithelia.

Functions

anchors epithelial cells

structural support

separates epithelium from connective tissue

influences behaviour/organisation

Cells attach to it via:

hemidesmosomes

focal adhesions

CAMs

20. Cell adhesion molecules (CAMs)

Transmembrane proteins that mediate:

cell-cell adhesion

cell-ECM adhesion

General properties

extracellular part binds CAM or ECM

intracellular part links to cytoskeleton

can be stable or dynamic

21. Main CAM types

Cadherins

cell-cell adhesion

usually homophilic

important in:

adherens junctions

desmosomes

Integrins

cell-ECM adhesion

bind laminin/fibronectin

important in:

focal adhesions

hemidesmosomes

Immunoglobulin superfamily CAMs

can do homophilic or heterophilic adhesion

22. CAMs in early development

E-cadherin expressed by two-cell stage

helps keep blastomeres together

helps organise early embryo

involved in implantation-related interactions

helps distinguish tissue layers

23. CAMs in tissue formation

CAMs are crucial for:

epithelial sheet formation

morphogenesis

cell aggregation

cell dispersion

delamination

migration

tissue boundaries

Example

Cadherins connect to actin at adherens junctions, allowing epithelial sheets to bend/reshape.

24. CAMs in gastrulation

During gastrulation, some epithelial cells undergo EMT:

lose strong adhesion

become motile

move inward

help form tissues like mesoderm

Later, cells may re-adhere and organise into structures like:

notochord

somites

25. Tissue sorting

Cells sort based on adhesion properties, especially cadherins.

E-cadherin cells group with E-cadherin cells

N-cadherin cells group with N-cadherin cells

This helps form:

tissue boundaries

organised layers

distinct embryonic structures

Ultra-crammed memory lines

No receptor = no response

Paracrine = local, endocrine = distant, synaptic = rapid, juxtacrine = direct contact

Morphogen gradient gives positional information

Apoptosis = shrink, bleb, fragment, no inflammation

Necrosis = swell, burst, inflame

ECM = support + signalling + migration scaffold

Connective tissue = cells + abundant ECM

Tight seals, adherens actin, desmosomes IF, gap communicate, focal adhesions actin-ECM, hemidesmosomes IF-basal lamina

Epithelium = packed, polarised, basement membrane, avascular

Mesenchyme = loose, motile, ECM-rich

Cadherins = cell-cell

Integrins = cell-ECM

EMT = lose adhesion, gain migration