Chapter 14- Mesoderm-paraxial and intermediate

1. Fig. 14.1- mesoderm lineages Recall lineages Notochord Lateral Intermediate Paraxial Circulatory, Body cavity, extraembryonic Kidney, gonads Head Somite Fig. 12.4 Cartilage, skeletal, dermis 24hr Fig. 14.2- mesoderm lineages in chick 48hr Chapter 14- Mesoderm-paraxial and intermediate

2. Paraxial Neural tube Head Somite Cartilage, skeletal, dermis Chapter 14- Mesoderm-paraxial and intermediate Paraxial mesoderm 4 components of somite formation • Periodicity- • somites form from cell groupings in regular intervals Fig. 14.3 • total number of somites is 50 in chicks, 65 in mice • Mechanism? Involves the hairy gene • Hairy gene expression correlates with positioning of somites • This effect is independent of all surrounding tissue 2. Epithelialization- mesenchyme is converted to epithelium prior to final somite formation • EM proteins fibronectin and N-cadherin link cells into clustered units

3. Paraxial mesoderm 4 components of somite formation (cont.) Paraxial 3. Axial specification • Distinct somites give rise to distinct structures Head Somite • Specific hox gene expression predicts the type of vertebra formed Cartilage, skeletal, dermis Somites hox5 hox6 hox9 hox10 Fig. 11.40-Mouse somites mapped to vertebrate regions and to specific hox gene expression 4. Differentiation- somites form 1) cartilage of vertabrae and ribs, 2) muscles of rib cage, limbs and back, and 3) dermis of the dorsal skin

4. Paraxial mesoderm 4 components of somite formation (cont.) Paraxial 4. Differentiation (cont)- somites form: 1) cartilage of vertabrae and ribs 2) muscles of rib cage, limbs and back 3) dermis of the dorsal skin Head Somite Cartilage, skeletal, dermis Fig. 14.7 Some somite cells become mesenchymal cells again to form sclerotome- these will become cartilage of vertebrae and ribs

5. Paraxial mesoderm 4 components of somite formation 4. Differentiation-(continued) Paraxial Somite has three additional regions that follow distinct fates Head Somite Cartilage, skeletal, dermis 1. Dermis A 2. Back muscles Fig. 14.9 3. Body wall Muscles B Sclerotome A Neural tube produces NT-3 and Wnt proteins that influence somite cell fate B Notochord produces sonic hedgehog to influence sclerotome fate

6. Myogenesis What dictates the muscle phenotype? Pax3 is a transcription factor that activates transcription factors Myf5 and MyoD Wnt? Pax3 Myf5 + MyoD Muscle-specific genes MyoD binding site Signaling pathway to activate muscle-specific genes (Fig. not in text) Introduction of MyoD into other cell types converts them to muscle Myoblasts fuse to form myotubes to produce muscle fibers Fig. 14.10

7. Osteogenesis (Bone development) What dictates the bone development? • There are three lineages that produce bone- • Somites (vertebrae/ribs) • Lateral mesoderm (limbs)- Not yet discussed • Cranial Neural crest (head/face) • Osteogenesis occurs by two mechanisms • Intramembrane ossification- bone withour cartilage precursor • Endochondral ossification- cartilage converted to bone 1. Intramembrane ossification Mesenchyme Neural crest cells Cell clustering Differentiate into osteocyte (bone cell) Differentiate into osteoblast (secrete collogen-proteoglycan matrix)

8. 1. Intramembrane ossification (cont.) Mechanism of intramembranous ossification) Transcription factor CBFA1 plays a key role BMP proteins also are important CBFA1 Mesenchyme Differentiate into osteoblast Activates expression of several bone-specific genes WT CFB1A -/- CFBA1 KO- all ossification prevented Blue- cartilage Red- Bone Fig. 14.12 Human disease- cleidocranial dysplasia (CCD)- due to mutaions in the CBFA1 gene

9. 2. Endochondral ossification B C Pax A cartilage Differentiate into chondrocytes Mesenchyme E D Proliferation ceases, matrix is modified Blood vessels invade, Chondocytes die Proliferate and form model of bone by producing an EM Adjacent cells (not chondrocytes) differentiate into osteoblasts to fill in bone A B C D E Fig. 14.13

10. Osteoclasts are cells which hollow out bones to form cavities • Osteoclasts enter through blood vessels • Osteoclasts are likely form blood-lineage precursors The disease ostroporosis occurs if too much osteoclast activity- bones become brittle The disease ostropetrosis occurs if too little osteoclast activity- bones are not hollowed out enough

11. Intermediate Mesoderm Fig. 14.1- mesoderm lineages Recall lineages Lateral Intermediate Paraxial Circulatory, Body cavity, extraembryonic Kidney, gonads Head Somite Fig. 12.4 Cartilage, skeletal, dermis Kidney development Three stages 1. Pronephric duct arises from intermediate mesoderm just ventral to anterior somites and migrate toward head

12. Kidney development Three stages 1. Pronephric duct arises from intermediate mesoderm just ventral to anterior somites and migrates toward tail Pronephros Nephric Duct 2. Migrating nephric duct cells induce mesenchyme to form pronephros(tubules) 3. Pronephric tubules degenerate, but a new set of mesonephros tubules are formed (approx 30 in humans) further down The mesonephros produces hematopoietic stem cells and, in some mammals, become sperm carrying tubes The metanephros tubules are formed from mesenchyme, which induces ureteric buds (these become ureters that transport urine from bladder) Fig. 14.18

13. Ureteric bud and metanephrogenic mesenchyme interact to become the kidney- called reciprocal induction Mechanism of reciprocal induction 1. Metanephrogenic mesenchyme formed 2. Metanephrogenic mesenchyme secretes GDNF and HGF to induce ureteric bud form Fig. 14.19 3. Ureteric bud secretes FGF2 and BMP2 to prevent apoptosis of Metanephrogenic mesenchyme 5. Metanephrogenic mesenchyme induces branching of ureteric bud 6. Differentiation and growth of the ureteric bud. 4. ureteric bud secretes LIF to induce mesenchyme cells to aggregate and become epithelial