Developmental Biology Unit 3

Juxtacrine Signaling

local signaling where membrane bound signaling protein receptors that bind to extracellular proteins of the membrane, both a interior and exterior protein

Homophilic binding

when one protein binds to the exact same protein

Heterophilic binding

where one protein binds to a protein of a different type

Paracrine Signaling

signaling proteins where the cell excretes signaling proteins/ligands that bind to receptor proteins on a different cell

Hormones

occur later in development and travel the greatest distance compared to other types of signaling

Cells and pH

cells separate and mix when introduced to pH and segregate when pH is removed, occurs with all types of cells

Selective affinity

cell types that have a positive or negative attraction to other cell types ex. Ectoderm has positive affinity for mesoderm and negative affinity for endoderm cells

Differential adhesion hypothesis

if A, then B, If B then C therefore if A then C; different cell types have different adhesive properties (varying levels of stickiness)

Cadherin

membrane spanning proteins that if removed/ blocked from synthesis would cause cell to disaggregate to become single cells/will stop clumping together; helps to determine morphogenesi

Surface tension

has linear relationship with cadherins where the more cadherins there are the more of this there is

Cells with a lot of cadherins

are attracted to cells with a lot of cadherin

N-cadherins

appear in mesenchymal cells right before the start of cartilage formation and disappear immediately after

E-cadherin

cadherin that all embryonic cells initially express until they become the neural tube, losing this expression

N-cadherin synthesis block

results in no proper border formation between the skin and the nervous system

Juxtacrine interaction

membrane proteins on one cell surface interact with the receptor proteins on an adjacent(or juxtaposed) surface

Paracrine interaction

when proteins synthesized by one cell can diffuse over small distances to induce changes in neighboring cells ( range of 15 cells)

Autocrine interaction

type of paracrine interaction where the inducer cells cerating the paracrine factors also respond to the factors. The cell creates the inducer and also has the receptor for that inducer

Morphogen four families

Fibroblast Growth Factor (FGF) family, the hedgehog family (sonic hedgehog), the WnT family, and the TGF_beta superfamily

Morphogen

paracrine factor that regulates gene expression; determines cell fate based on concentration

Paracrine factor functions

either regulates transcription factor or regulates the cytoskeleton (remodeling) to allow the cell to migrate; these concepts are called signal transduction cascades

Bead experiment

control with no activin on middle beads, low concentration(1nM) of activin caused beads around middle to express Xbra, high concentration 4(nM) middle caused beads in direct contact to express goosecoid and beads around it to express Xbra

Exocytosis

one mechanism used to eliminate a receptor protein at the membrane

Paracrine factors (like wnt)

are affected by different proteins

Wingless (Wg) expression

the mutation of this results in drosophila that don’t have wings, paracrine factor/gene

Swim

protein that stabilizes wingless paracrine factor and helps it to diffuse a further distance

Distal-less expression

activated by wingless that can be messed up by swim mutation

Fibroblast Growth Factor(FGF)

how secretion of the protein heparan sulfate proteoglycans (HSGP) can influence paracrine factor diffusion with this family; can modulate, reduce, or increase the diffusion

Five mechanisms for shaping FGF8 gradient

difference in transcription, free diffusion, HSPG directed diffusion(Speeds up diffusion), Diffusion confined by HSPG clustering(slows diffusion), and FGF8 complex internalized by endocytosis and targeted for degradation

Cillium

small protrusions in the cell that host some of the receptors since receptors aren’t everywhere on the cell membrane

Receptor tyrosine kinase(RTK)

receptor that FGF will bind to; spans from the extracellular matrix into the cytoplasm, changes form when in contact with ligand causing phosphorylation w/ ATP that is used to phosphorylate the protein

HSPG

extracellular glycans that help the diffusion of paracrine factors

Prolactin

causes the dimerization of prolactin receptors in the mammary duct epithelial cells

Thanatophoric dysplasia

failed bone growth where all the bones are truncated (short)

IHOG

interference hog, dimer protein (protein molecule composed of two protein subunits)

Boi

brother of interference hog, dimer protein

Gas1 and Boc/Cdo

membrane bound proteins that help to catch sonic hedgehog

Patched

transmembrane protein that, when there is no SHH, represses smoothened

PKA/Gli microtubule complex (no SHH)

Gli is phosphorylated by PKA which causes Gli to be dimerized (cut in half) with the halves moving into the nucleus to act as transcription repressors

Sonic Hedgehog

binds to the patched protein, entering the membrane with patched, preventing smoothened from deactivating patched and stops the microtubule apparatus from splitting Gli so whole Gli activates gene transcription

TGF Beta

superfamily with a lot of receptors that combine multiple ligands, has 2 dimers

Glypicans

catch wnt and concentrate them, gathering them from extracellular matrix to increase concentration of wnt, also binding to frizzled

Wnt & frizzled binding

causes secretion of Notom

Notom

cuts off wnt and removes its associated lipids preventing wnt from binding to glycans or frizzled

No Wnt

Binds beta catenin to TCF and

Ubiquitin

tag that targets for degradation and breaks down APC when no wnt is present

With wnt

binds to frizzled and Lrg/LRP ⅚, frizzled binds to disheveled which turns into an inhibitor of GSK3, allowing APC to be free and beta catenin to bind to TCF allowing transcription to occur

Beta catenin

downstream transcriptional effector of wnt signaling

Extracellular matrix

an insoluble network consisting of macromolecules secreted by cells.

Extracellular matrix components

protein collagen proteoglycans, and specialized glycoproteins (such as fibronectin and laminin)

Cell adhesion, migration, and epithelial sheet formation

all depend on cells forming attachments with extracellular matrices

Fibronectin

large glycoprotein which is an adhesive molecule linking cells to one another and to other substrates; has multiple binding sites that when binded to create proper orientation of the cells in the extracellular matrix and lines roads for cell migration

Laminin and type IV collagen

make up the basal lamina

Basal lamina

form closely knit sheets that underlie the epithelial tissue

Integrins

receptors for extracellular matrices molecules that integrate the extracellular matrix with the cell by binding proteins; named because they integrate the interior and exterior scaffolds

main fibronectin receptor binds fibronectin, spans the membrane of the cell and links to the actin cytoskeleton, linking exterior and interior scaffolding

Integrins signal…

from outside the cell to inside the cell causing changes in gene expression

Actin

microfilament that organelles move across and proteins can be transported across “highway system inside the cell”