BIO230 Lecture 4-6 (How do multicellular organisms develop)

lecture 4, lecture 5, lecture 6

what are the three key processes in multicellular development

1. cell proliferation

2. cell differentiation

3. cell morphogenesis

what is cell proliferation

cell division

what is cell differentiation

change in cell fate initiated via cell signalling and differential genome expression

what is cell morphogenesis

change in cell shape, interactions and or location

what is embryogenesis

initial stages after egg fertilization

to go from fertilized egg to blastula what needs to happen

cell proliferation (need to divide to make more)

to go from blastula to gastrula what needs to happen

cell differentiation and cell morphogenesis

how can morphogenesis occur (3 ways)

1. cell internalization

2. elongation

3. fine repositioning of cells

what is gastrulation 

change from ball of cells to embryo with a gut and 3 germ layers of tissues which can then go onto form different parts of the body

what are the three tissue layers that forms from gastrulations

ectoderm→ epidermis and nervous system (outside)

mesoderm → muscles, connective tissue, bones, blood, kidneys etc (inside)

endoderm → gut, lungs, pancreas, liver, etc (very inside)

how is the mesoderm formed

cell internalization by ingression/delimitation

what is ingression/delimitation

ingression → individual cells detach (blastula cells loss adhesion) from the outer cell layer and migrate in where they are no longer tightly adhered to eachother

delamination → these cells form a new layer called the mesoderm 

what is a epithelial to mesenchymal transition refer to

ingression → individual cells detach (blastula cells loss adhesion) from the outer cell layer and migrate in where they are no longer tightly adhered to eachother

why do epithelial to mesenchymal transitions need to be carefully controlled

to make sure correct cells are detached. e.g. if tumor cells can detach they can establish other tumors 

how is the endoderm formed

invagination/involution

what is invagination/involution

invagination→ attached cells in an epithelial cell sheet are pulled into the middle of the embryo while remaining attached

involution → these cells curl in and grow to form the endoderm 

what does ivagination/involution require and why

1. actin → constricts at top of cells and cells maintain tight contact

2. cell adhesion → maintains integrity, direction

what are the two mechanisms of elongation for morphogenesis

1. convergent extension (cell movement)

2. asymmetric growth (no movement)

what is convergent extension

cells migrate to line along axis of organism (makes organized) 

1. cells converge, or crawl together (collective cell migration)

2. cells extend, or form a line 

chain-type migration vs sheet-type migration

chain type involves less adherent cells and sheet-type involves more adherent cells

explain how cellulose can lead to directional expansion

cellulose constricts plant cell expansion thus forcing expansion in one direction (i.e. leading to elongation)

what guides plant cell wall deposition (explain the organization and elongation pattern 

microtubules

organized microtubules (=organized cellulose)→ directional elongation

disorganized microtubules (=disorganized cellulose)→ no directional elongation (swelling)

what are the two types of fine repositioning of cells

1. whole cell migration

2. part migration 

how does whole-cell migration occur

whole cells migrate twds the tup of the radial glial cell, first born neurons are deeper layers and last born neurons are in the outer layer

what is cell differentiation

the acquisition of specialized cell functions via differential genome expression

what are the two ways that cells can differentiate

1. asymmetric division → child cells born with different fates

2. symmetric division then perception of a signal → child cells born the same but acquire different fates 

explain asymmetric division in terms of cell fate and what is required 

cell fate markers are unevenly distributed before division and after division one child cell will inherit more of this cell fate marker

• requires correct spindle alignment and cytokinesis 

after symmetric division (cells are the same), what differentiates the cells (3 ways), explain each way

1. lateral inhibition → a tiny or short lived difference between two cells tips the balance and molecular mechanisms amplify the difference till the cells have eventually acquired different fates ~ the one that makes slightly more begins to inhibit the other one

2. induction by diffusible signals → morphogen gets secreted which causes cells to respond and take on a new fate- creates ring or band patter

3. other mechanisms 

what type of inhibition is notch signalling, explain what notch signaling is

lateral inhibition

• All cells start with both Delta and Notch; they activate each other's receptors reciprocally to prevent specialization.

  • Eventually one "winner" cell accumulates more Delta than its neighbors. Its high levels of Delta strongly activate Notch in surrounding cells.

  • Activated Notch blocks those neighbors from differentiating or producing more Delta themselves.

  • The winner cell keeps high levels of Delta but inactive Notch; thus it differentiates (such as becoming a bristle), while all surrounding "loser" cells have active Notch but no Delta and stay undifferentiated.

NOTE: notch inactivates delta 

how do morphogens work

in an organizer tissue, a cell can secrete a morphogen which is diffusable and can acton nearby cells causing them to take on a new fater- because diffusable to nearby it makes band or ring patters 

what does morphogen diffusion rate depend on

how much morphagen is made and for how long

diffusion rate of signal

stability of the signal 

why cant morphagens be indefinitely active

Cells retain a "memory" of the morphogen's influence through stable changes in their regulatory networks.

• If morphogens were indefinitely active, cells would remain plastic and could keep changing their identities, which would disrupt the formation of organized tissues and structures during development.

• Continuous activity could also lead to abnormal growth or patterning errors because cells might not stabilize into their intended fates.

• The stability or degradation rate of morphogens ensures that signals are limited in time and space, allowing precise control over developmental processes.

• Proper tissue patterning requires that once cells have responded to a morphogen gradient and adopted new identities, they stop responding so that spatial patterns become fixed.

explain how transplant experiments can identify organizer tissues

• Organizer tissues secrete diffusible signals - morphogens

• When organizer tissue is transplanted, it can impose its fate-directing signals on naive host cells.

• If new structures form at the transplant site (such as a second body axis), this demonstrates organizing activity.

• In contrast, transplanting non-organizer (ventral) tissue does not change development because these tissues do not produce fate-directing signals; they simply respond to existing organizers.

what is totipotent

cells can become any cell type (cells at early fertilization)

what is pluripotent

cells that can become any adult cell type e.g. blastomeres

what is multipotent

cells that can become multiple cell types. e.g. ectoderm, mesoderm, endoderm

explain sequential signaling vs combinatorial signaling

• Sequential signaling relies on stepwise integration over time with each new signal building upon previous ones.

• Combinatorial signaling depends on simultaneous integration of multiple signals at once.

both are mechanisms by which cells interpret fate-directing signals during development

what does it mean by sequential signaling can generate regulatory hierarchies

gene regulation that affects another gene regulation that affect another genes regulation etc.

how do multiple signals overlap to create complex patterns

through transcription factors 

how do hox genes determine which body parts develop from a segment

they act as transcription factors, they are expressed in different segments and specify different body parts, they are organized on chromosomes in order of expression into a hox complex, 

what does loss or gain of function hox gene cause (misexpression)

if Hox gene is misexpressed outside its normal domain—such as expressing a leg-patterning gene where antennae should form—it can cause abnormal development like legs growing where antennas would be expected. This shows how crucial precise regulation is for normal patterning.

what is cellular turnover

cell division and cell death - amount depends on cell type and tissue

what cell types cannot be renewed

sensory cells with specialized architecture

e.g. photoreceptor and auditory cells

explain why even non-renewable cells undergo molecular turnover

Non-renewable cells cannot be replaced through division but continuously renew their internal molecules by synthesizing new RNAs and proteins while degrading old ones. This process allows them to maintain function despite being unable to regenerate if lost.

how do non renewable cells undergo molecular turnover

1. a pulse of radiolabeled leucine is supplied to non-renewable cells 

2. the leucine is incorporated into new proteins in a new photoreceptive disc

3. more new proteins are made and new discs move into the outer segment

4. the labeled proteins are pushed up the outer segment

5. at the end of their life the labeled proteins are removed from the cell

what are traits of stem cells

• can divide indefinitely

• are not terminally differentiated

• can self renew

• can differentiate

why must stem cell divisions and stem cell fate be carefully regulated

the more a stem cell divides in a particular tissue, the greater the risk of cancer in that tissue

what do internal stem cell fate determinants do

they help determine things being stem cells

can either be

• asymmetric division

• symmetric division 

explain what happens when a stem cell undergoes symmetric vs asymmetric division (internal factors)

symmetric → both become stem cells

asymmetric → one stays stem cell one becomes differentiated

• the cell fate determinant is localized to one side of cell and keeps that one stem

NOTE: asymmetric division doesn’t make more stem cells

what are ways a stem cells fate can be determined

• external factors ie the environment

• stem cell niches can promote self-renewal (e.g. secreted signal molecules, direct cell-cell contact → if a cell leaves the niche it will differentiate, cell that remains in contact with niche will remain a stem cell (cell-cell contacts)

why do stem cells divide slowly

it protects cells from random mutations from DNA replication and telomere depletion

what do transit-amplifying cells do

divide rapidly to increase cell numbers before final differentiation

• a stem cell makes a progenitor cell, this cell then divides rapidly, the stem cell does not itself 

what is unipotent

can produce only one cell type

what is terminally differentiated

fully differentiated and will not usually divide again

how does the epidermis display concepts of stem cells

the basal lamina provides a stem cell niche, the cells divide via symmetric divisions, transit amplifying cells undergo many divisions and migrate into the prickle-cell layer

cells differentiate further in the layers and dead cells flake off from the surface

how are step cell concepts exemplified in the blood

transit amplifying cells increase cell numbers before final differentiation and slow stem cell self-renewal protects stem cells 

how were hematopoietic stem cells identified, what was found about multupotent stem cells 

transplantation experiments

• transplant of 1 multipotent stem cell can restore all blood types, including stem cells - bone marrow contained blood stem cells

draw backs embryonic stem cells

draw backs

• ethical concerns

• immune rejection

• potential for cancer to develop

what is the difference between a pluripotent embryonic stem cell and a differentiated adult cell from the same individual 

they have the same genome but different genome expression 

how can induced pluripotent stem cells (iPS)  be made from regular adult cells 

changes in genome expression through OSKM factors (transcription factors ) . exposing iPS to different factos can trigger differentiation