Formation III Morphogenesis: building 3D structures 7.013 4.6.07 Formation III Morphogenesis: building 3D structures

LIFE START FUTURE How-to 2 PROBLEMS FORMATION SYSTEMS How-to 1 BIOLOGY STEM CELLS, CLONING LIFE FUTURE How-to 2 VIRUSES 3D STRUCTURE IMMUNE NERVOUS PROBLEMS CANCER POSITION &FATE SYSTEMS FORMATION REC. DNA How-to 1 HUMAN DISEASE STEPS BIOCHEM GENETICS MOL. BIO CELL BIO. START FOUNDATIONS

20 V D V D Dorsal determination Egg b-catenin phosphorylated H. Sive MIT 2007 20 Dorsal determination See Purves 20.3 V D Egg b-catenin phosphorylated unstable, cytoplasmic V D 2-4 cells and older: determinants inhibit b-catenin phosph. dorsally stable, nuclear determinant

(High Nodal induces endoderm) H. Sive MIT 2007 22 Nodal binds receptor that activates Smad2 txn factor animal pole mesoderm Low Nodal induces mesoderm 500+ cells (High Nodal induces endoderm) 2 - 500+ cells LO HI vegetal pole Nodal (ligand) gradient Mesoderm determination Nodal ligand

+ = 23 V D animal pole 500+ cells 500+ cells low Nodal b-catenin H. Sive MIT 2007 23 500+ cells 500+ cells + low Nodal V D b-catenin Mesoderm Dorsal dorsal mesoderm: b-cat + low Nodal (Smad2) activates MyoD transcription = Dorsal mesoderm = future muscle 4,000+ cell stage vegetal pole

Somites: Segments that will form muscle, skeleton and skin

Biological 3D structures

1 Specialized cell shape: neuron

2 Organ: kidney

3 Lab Grows Bladders From Cells of Patients Washington Post Tuesday, April 4, 2006

4 egg (0hpf) early blastula (4hpf) late blastula (8hpf) H. Sive MIT 2007 egg (0hpf) early blastula (4hpf) late blastula (8hpf) division, determination Stages in Xenopus development gastrula (11hpf) movement neurula (16hpf) tadpole (40h) differentiation first structures

5 What processes would turn the pile of cells (blastula) 3D structure (organ) What processes would turn the pile of cells into a 3D structure? (about 6)

6 Epidermal Epidermal Epidermal cells Epidermal cells cells cells Cell type sorting Reaggregation Cell dissociation Neural plate cells Epidermal cells Outside Neural inside Cell sorting due to differential and homotypic cell adhesion (N-Cadherin vs E-cadherin)

7 Epithelium/mesenchyme and transition apical Epithelium: cell sheet junctions basal extracellular matrix (ECM) Mesenchyme: single cells H. Sive MIT 2007

Shape and movement: role of cytoskeleton

8 Platelets changing shape during clotting resting clotting G-actin unpolymerized F-actin polymerized From Molecular Biology of the Cell/ Lodish

9 Actin polymerization during cell movement From Molecular Cell Biology/ Lodish Zone of actin polymerization Front/ leading edge Direction of movement nucleus Rear/ trailing edge Lamellipodia/filopodia Actin polymerization during cell movement

Rearrangement of microfilaments (F-actin) 10 Rearrangement of microfilaments (F-actin) with cell movement

Receptors connect ECM and cytoskeleton 11 See Purves 4.26 Receptors connect ECM and cytoskeleton cells cytoskeleton receptors ECM proteins proteoglycans Adhesion receptors: integrins ECM proteins: collagen, laminin, fibronectin H. Sive MIT 2007

12 Cell adhesion and signaling Rear (trailing edge) adhesion loss Front (leading edge) increased adhesion F-actin nuc receptor ECM ligand focal adhesion movement ligand (laminin) binds receptor (integrin) which activates Focal Adhesion Kinase activates GTPase (rac/cdc42/rho) activates profilin which increases F-actin H. Sive MIT 2007

Epithelial sheets and building tubes

13 apical columnar cuboidal squamous wedged basal Cell shape changes via cytoskeleton Flat epithelial sheet Bent epithelial sheet

14 Epithelial sheets can roll or bend to form a tube Examples: brain, spinal cord

Amphibian neural tube forms by rolling up an epithelial sheet 15 Ray Keller Amphibian neural tube forms by rolling up an epithelial sheet

16 Mesenchymal cells can condense to form a tube Examples: blood vessels, some kidney tubules

17 Purves 48.12: Lung tubules

18 Lung tubule branching: initial steps

19 An epithelial sheet can extend to form a tube Example: primary tracheal tubules

20 Single cells can roll or hollow into tubes Examples: secondary and terminal tracheal tubules

Primary tracheal outgrowth and branching (Drosophila) 21 FGF inhibitor = sprouty FGF (ligand)= branchless FGF receptor = breathless epithelium Primary tubule Secondary Terminal O2 stress genes Primary tracheal outgrowth and branching (Drosophila) See Purves 48.5

22 Tubule morphogenesis in culture

23 FGF = ligand Receptor (tyrosine kinase) 15.11 Purves: 15.9: Fibroblast Growth Factor signaling