model organisms and development 2

cell proliferation

single cell replicates and divides to produce many cells

cell differentiation

different cells express certain genes to become distinct from one another

cell morphogenesis

cells change shape and move to interact with one another

first days of mammalian development

1. zygote is formed following fertilization

2. 2 days post-fertilization: major zygotic/embryonic genome activation (EGA) to replace maternal mRNAs

3. 3-4 dpf: compaction to increase cell adhesion, creating smooth and round appearance

4. 4-5 dpf: cavitation (blastocoel formation)

5. 6 dpf: expansion and hatching

6. 7-10 dpf: implantation

blastocoel

asymmetric fluid-filled cavity containing inner cell mass

cleavage divisions

• cutting cell in half to generate new cells

• total mass remains the same, even as number cells increase

totipotent

can become any cell/tissue

trophectoderm

becomes extraembryonic tissues (including placenta)

inner cell mass

becomes embryonic tissues (including fetus and yolk sac)

early cell differentiation of inner cell

• content cells on all sides (surrounded)

• LATS1/2 (kinase) phosphorylates YAP/WWTR (transcription factor), inactivating it

• YAP/WWTR cannot bind target (TEAD4), cannot activate transcription of certain genes

early cell differentiation of outer cell

• one surface with no cell contact (contacts ECM)

• LATS1/2 held at membrane by F-actin

• YAP/WWTR binds target (TEAD4) and activates transcription of certain genes

• signaling cascade specified cell identity

epiblast gastrulation

• primitive streak forms

• cells migrate through primitive streak, differentiate based on order of migration

• cell that migrate first become endoderm

• cells that migrate second become mesoderm

• cells that remain in epiblast (do not migrate) become ectoderm

ectoderm

• outer surface (epidermal cells of skin)

• central nervous system

• neural crest (pigment cell)

mesoderm

• dorsal (notochord)

• paraxial (bone tissue)

• intermediate (tubule cell of kidney)

• lateral (red blood cell)

• head (facial muscle)

endoderm

• digestive tubule (stomach cell)

• pharynx (thyroid cell)

• respiratory tubule (alveolar cell)

three main body axes established by gastrulation

• anterior-posterior: no primitive streak in anterior

• dorsal-ventral: primitive streak on dorsal face, cells migrate ventrally

• left-right: established based on anterior-posterior axis

ultrabithorax (Ubx) mutants

• loss of Ubx → missing halteres, two pairs of wings

• gain of Ubx → no wings, two pairs of halteres

fluorescence in situ hybridization

probe is labeled with fluorophores, fluoresces when bound to target mRNA

Hox genes

• control anterior-posterior patterning

• present in same order as they are expressed and order of positional identity on chromosome(s)

overexpression of HoxA10 in all vertebrae in mice

all vertebrae become lumbar (not attached to ribs)

loss of HoxA10 in all vertebrae in mice

lumbar/sacral vertebrae become thoracic (attached to ribs), anteriorization

planar cell polarity

• cells lay flat contain certain components at either proximal/anterior or distal/posterior poles

• through cell contacts, other cells share same A-P axis

• in mice, all hair follicles point towards the posterior

neural tube

• gives rise to central nervous system

• anterior → brain

• posterior → spinal cord

• dorsal-ventral patterning is essential to build neural circuits

morphogens

• diffusible signals that exert graded effects

• cellular response depends on how far cell is from source of gradient

• ex: Shh, BMP, TGFβ, Fgf, Wnt

morphogens in neural tube

• BMP gradient strongest in dorsal side

• Shh gradient strongest in ventral side

combinatorial signaling

different combinations and levels of different morphogens cause different differentiation in cells

cellular memory

previous signals are retained (change of organization in genome) such that cells that have encountered different signals but are presented with the same new signal respond differently

cell growth

individual cells increase in size

cell division

cells divide in two, generating more cells

Yorkie/YAP pathway

LATS1/2 -| Yorkie/YAP → Myc (growth), Cyclin E (division), Diap and Bantam (survival) → tissue growth

YAP overactivity in mouse liver

overgrowth

Yorkie/YAP overactivity in fly head

giant, bulbous