Signal Integration

Simple Signaling

One hormone produces one function.

ACh

Stimulates secretion from salivary gland epithelia through G-protein-coupled receptor linked to a Gq-PLC-IP3-Ca2+ pathway.

cAMP Levels

Dictated by simultaneous activation and inhibition of adenylyl cyclase by Gas and Gai

Cell with Signal Pathways 

Constantly receiving information from multiple signal pathways

Tissue Homeostasis

Well-orchestrated control of cell populations and fate through modulation of differentiation, proliferation and apoptosis

Stem Cell Input

Cell numbers can be altered by increased or decreased rate of this cell

Apoptosis

Cell death

Cell Numbers Effected

Stem cell input, apoptosis, proliferation, and differentiation

Different Signals

Different signals cause different actions within the cell (survive, divide/proliferate, differentiate). No signal causes cell death.

Essential Cellular Functions During Development

Cell proliferation, cell specialization, cell interaction, and cell movement.

Neural Crest Cell Migration and Differentiation

1. Dedifferentiation-epithelial to mesenchymal (cells that will become neural crest cells)

2. Proliferation (neural crest cells)

3. Migration of neural crest cells

4. Aggregation and then differentiation/specialization

Conserved Theme

Tissue initiation and morphogenesis involving communication between ectoderm and mesenchyme 

Tissue Initiation

1. Ectoderm

2. Epithelial placode

3. Epithelial Bud

Tissue Morphogenesis

1. Skin ectoderm-derived organs (hair follicle and mammary glands)

2. Oral ectoderm-derived organs (tooth and salivary gland)

FGFR

Branching morphogenesis of salivary glands

Disruption of Salivary Gland Development

Caused by mutations of multiple signaling genes varying from FGF. EGFR, Edar

Mesenchyme

Matrix + mesenchymal cells

Inputs for Salivary Gland Development

1. Initial epithelial bud is promoted by FGFR to become pseudoglandular

2. EDA/EDAR Shh/Ptc causes branching of gland

3. EGFR BMPs and VIP cause salivary gland to be completely

Epithelium and Mesenchyme Interactions

1. FGF receptors on mesenchyme cells and on bud epithelium cells

2. Sonic hedgehog (Shh) is produced by epithelial cells at the tip of the growing bud, causing inhibition of FGF10

3. Two new centers of FGF production were created (split by the inhibition of Shh)

4. Two new buds are formed, causing branching morphogenesis of ducts.

Signaling Tooth Development

1. Initiation 

2. Morphogenesis

3. Differentiation and mineralization

4. Root formation and eruption

5. Caused by a series of signaling between different cell types generating adult structure

Tooth Engineering

Signaling between mesenchyme and epithelial cells could be co-opted for making teeth. 

Craniosynostosis and Achondrioplasia

Disorders driven by overactivity of FGFR (receptor tyrosine kinase). FGFR mutations fix receptor kinase activity in the on position. Proliferation of chondrocytes is inhibited, hypertrophy is accelerated, and the growth plate does not expand normally.

CNP

Act as a go switch for bone growth

FGFR Signal

Signals to stop boen growth

FGFR and CNP/NPRB

Balance between the two is crucial for normal bone growth (stop and start growing). Gain of gain-of-function mutation in FGFR causes inhibition of endochondral growth.