Bio 132 Lecture 10 Mesoderm - Somite 2024 PDF

MESODERMAL STRUCTURES LERRIE ANN IPULAN-COLET G I L B E RT A N D B A R R E S I 1 1 TH E D SOMITOGENESIS: DIRECTIONALITY AND SIZE 1.Is there directionality to the creation of somites? 2. Are they of same size? 3. Which is the older somite, SIV or SI? BOUNDARY FORMATION 1. What events are neces...

MESODERMAL STRUCTURES LERRIE ANN IPULAN-COLET G I L B E RT A N D B A R R E S I 1 1 TH E D SOMITOGENESIS: DIRECTIONALITY AND SIZE 1.Is there directionality to the creation of somites? 2. Are they of same size? 3. Which is the older somite, SIV or SI? BOUNDARY FORMATION 1. What events are necessary for A/P elongation of somites? 2. What signal inhibit somitogenesis and what signal induce it? 3. Which signal is responsible for epithelialization of somites? 4. What morphogenetic/cellular event is necessary for epithelialization? ANALOGIES IN SOMITOGENESIS morphological – pandeasal/bread making, candy, chorizo/longanisa, plants nodes/internodes, molecular – toxic jowa, sunscreen/sunburn, PARTITIONS AND LINEAGES OF THE MESODERM  SOMITE FORMATION Epithelialization-caused by expression of fibronectin and cadherins which may in turn be brought about by the transcription factor, Paraxis Specification (axial specification occurs early in development; e.g. only certain somites form ribs) Epithelial Mesenchymal Transition (EMT) Differentiation within somites WATCH BARRESSI VIDEO SOMITE DETERMINATION  EMT IN THE SOMITE Pax1 – migrating scleretome Lose N-cad Inhibitors of MRFs EPIMERE/SOMITES Divides into – Sclerotome Development vertebrae development bone development – Dermomyotome Development Myotome Dermatome migrating myoblast  SOMITE DIFFERENTIATION D A E B C 1. Collective term for A? 2. Collective term for B? 3. What structures would D contribute? 4. What would cells in E contribute to? 5. What would cells in C contribute to?  SOMITE DIFFERENTIATION D A E B C 1. Collective term for A? Syndetome (tendons) 2. Collective term for B? Arthrotome (vertebral joints) 3. What structures would D contribute? spine and arch 4. What would cells in E contribute to? distal rib 5. What would cells in C contribute to? vertebral body and BV SOMITE DIFFERENTIATION  Repatterning of sclerotome for formation of vertebrae TGFB Receptors Secretes PDGF Attracted to the Induces surrounding notochord mesenchyme to release Epimorphin Repatterning of sclerotome for formation of vertebrae OTHER STRUCTURES FROM SCLEROTOME TENDONS – Scleraxis-expressing part of the scleretome (syndetome) DORSAL AORTA – posterior sclerotome origin of ECs and vSMCs – other arteries are from lateral plate mesoderm – EC differentiation is induced by Notch sig in Ephrin B2-dependent manner EPIMERE/SOMITES Divides into – Sclerotome Development vertebrae development bone development – Dermomyotome Development Myotome Dermatome migrating myoblast E14.5 E16.5 Rigueur and Lyons, 2014 SEGMENTAL ARRANGEMENT OF VERTEBRAE Role of Hox genes expression in anteroposterior patterning of vertebral column Roles of spinal ganglia and notochord in morphogenesis and segmentation of vertebral column Skeletal development: Endochondral and Intramembranous ossification  Endochondral Ossification http://www.ncbi.nlm.nih.gov/books/bv.fcgi?db=Books&rid=dbio.section.3479  ENDOCHONDRAL BONE FORMATION I. involves the invasion of the cartilage model by blood vessels. The hypertrophic chondrocytes die by apoptosis. Osteoblasts in periphery encroach and deposit bone matrix 1I. mesenchyme (in sclerotome,limbs,) is induced to secrete Pax 1 and Scleraxisàactivate cartilage specific genes III- the chondrocytes proliferate rapidly to form the model for the bone. As they divide, chondrocytes secrete a cartilage-specific extracellular matrix.  THE ENDOCHONDRAL BONES (CONT’D) IV. Committed mesenchyme cells condense into compact nodules and differentiate into chondrocytes – N-cadherin - important in the initiation of these condensations, and N-CAM seems to be critical for maintaining them V. cells become hypertrophic chondrocytes which alter the matrix they produce (by adding collagen X and more fibronectin) so that mineralized calcium are easily deposited  ENDOCHONDRAL BONE FORMATION First phase- mesenchyme (in sclerotome,limbs,) is induced to secrete Pax 1 and Scleraxisàactivate cartilage specific genes Second phase-Committed mesenchyme cells condense into compact nodules and differentiate into chondrocytes – N-cadherin - important in the initiation of these condensations, and N-CAM seems to be critical for maintaining them  THE ENDOCHONDRAL BONES (CONT’D) Third phase - the chondrocytes proliferate rapidly to form the model for the bone. As they divide, chondrocytes secrete a cartilage- specific extracellular matrix. Fourth phase cells become hypertrophic chondrocytes which alter the matrix they produce (by adding collagen X and more fibronectin) so that mineralized calcium are easily deposited  THE ENDOCHONDRAL BONES (CONT’D) Fifth phase involves the invasion of the cartilage model by blood vessels. The hypertrophic chondrocytes die by apoptosis. Osteoblasts in periphery encroach and deposit bone matrix  Endochondral Ossification http://www.ncbi.nlm.nih.gov/books/bv.fcgi?db=Books&rid=dbio.section.3479 ENDOCHONDRAL BONE DEVELOPMENT Provot and Schipani 2004  ENDOCHONDRAL BONE DEVELOPMENT Sox Trio – master regulator of early chondrogenesis - commitment of mesenchymal cells to cartilage (Sox 9) - secretion of critical collagen ( Sox 9) - Sox5 and 6 deficient mice has chondroplasia BMP - mesenchymal condensation - Pro-proliferation and anti-differentiation Provot and Schipani 2004  ENDOCHONDRAL BONE DEVELOPMENT FGFr3 – accelerate chondrocyte proliferation and differentiation - constitutive active mutations result to skeletal dysplasia ex, short limbs and dwarfism PTHrP – gate keeper of zone of hypertrophic chondrocytes - control the switch from proliferative immature chondrocyte to post-proliferative mature hypertrophic chondrocyte Provot and Schipani 2004  ENDOCHONDRAL BONE DEVELOPMENT Ihh – central coordinator of endo bone dev - inhibits hypertrophic chondrocyte differentiation - stimulates proliferation and PTHrP Runx2,3*, CBFB master inducers of chondrocyte hypertrophy - proper rate of chondrocytes hypertrophy and maturation. Provot and Schipani 2004 ENDOCHONDRAL BONE DEVELOPMENT Provot and Schipani 2004 RUNX`S NEW ROLE Runx2 is essential for specifying the osteoblast lineage and directly regulates another transcription factor, osterix (Osx) but is also expressed by HCs. It regulates Col10a1 and matrix metalloproteinase-13 (Mmp13) expression in HCs. Osx is expressed in prehypertrophic chondrocytes and osteoblasts and is essential for preosteoblast differentiation by transactivating Col1a1, which encodes collagen I, a marker of differentiated osteoblasts. Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation Liu Yang, K. Tsang, Hoi-ching Tang, D. Chan, K. Cheah Proceedings of the National Academy of Sciences of the United States of America THE GROWTH PLATE AND HORMONAL INFLUENCE Influenced by growth hormone and IGF At puberty growth spurt is due to sex hormones which also causes the closure of the growth plate eventually. – Absence of sex hormone (estrogen)àosteoporosis in menopausal women DEVELOPMENT OF DERMAL BONES derived from intramembranous ossification skull, jaws, gill covers, fin spines rays, shell Human Skull : from both NCC and mesoderm – BMP2, 4, and 7 from the overlying epidermal ectoderm induce neural crest cells of the headàexpression of cbfa genes- transcription factor that leads to expression of bone specific ECM proteins E14.5 E16.5 Rigueur and Lyons, 2014 DEVELOPMENT OF DERMAL BONES Anatomy and Physiology by Biga et al., 2022 cellbio.utmb.edu/microanatomy/bone/intramembr... DEVELOPMENT OF THE THE SKULL D-V Patterning (Chick model) - FEZ / Frontonasal ectodermal zone - midfacial ectoderm coordinates frontonasal and plate development - Fgf8 and Shh boundary Schilling and Pabic , Human Osteology, 2012 DEVELOPMENT OF THE THE SKULL C. Osteo progenitors migrate and add to the leading edges of developing bones D. Signaling that affects suture maintenance for further growth - Bmp – bone formation - Jag1 – osteogenic font - Twist - mifration Schilling and Pabic , Human Osteology, 2012 WHAT IS CRANIOSYNOSTOSIS? EPIMERE/SOMITES Divides into – Sclerotome Development vertebrae development bone development – Dermomyotome Development Myotome Dermatome migrating myoblast EPIMERE/SOMITES Divides into – Sclerotome Development vertebrae development bone development – Dermomyotome Development Myotome Dermatome migrating myoblast  DERMOMYOTOME DEVELOPMENT FGF signals from myotome activate Snail2 in the central DM CENTRAL DERMOMYOTOMES CENTRAL -creates dermal cells and muscle precursors of the back and BROWN FAT – Bmp7 induces TF PRDM16, which is necessary for conversion of myoblasts to brown fat cells DML – primaxial muscles VLL – abaxial muscles – regulated by MRFs ie.,MyoD, Myf5,myogenin, MRF4 EPIMERE/SOMITES Divides into – Sclerotome Development vertebrae development bone development – Dermomyotome Development Myotome Dermatome migrating myoblast PARTITIONS AND LINEAGES OF THE MESODERM DIFFERENTIAL GENE EXPRESSION IN MUSCLES http://7e.devbio.com/images/ch05/0504fig5.gif KISS AND RUN AT DM LIPS Rios et al. 2011 K I S S A N D R U N AT DM LIPS -Unique dispersal of signaling (Delta, Wnt) -Regulation of myotome Delta/Notch – differentiation into myotome Wnt1 – upregulates Wnt11 and organizes myotome - Nc secretes neuregulin-1 to maintain myogenic progenitor pool MYOGENESIS OF SKELETAL MUSCLE FIBER HOW SKELETAL MUSCLE ORGANS ARE FORMED Formation of non specific muscle masses Muscle masses break up into discrete units which become the primordia of individual muscles Differentiation of myotubes from myoblasts Innervation – Motor innervation – Sensory innervation-àformation of intrafusal fibers of the muscle spindle FACTORS REGUL ATING MUSCLE DEVELOPMENT m Insulin-like growth factor-1 and –2 § Stimulates proliferation § Stimulates differentiation m Fibroblast Growth Factor § Stimulates proliferation § Inhibits differentiation m Transforming growth factor beta § Suppresses proliferation § Suppresses differentiation § Negative regulator myostatin http://dayton.fsci.umn.edu/~bill/differentiation.jpg www.ans.iastate.edu/.../reecy/reecyfocus.html  CATEGORIZING FACTORS THAT CAN AFFECT MYOGENESIS List down the factors discussed under category A or B. Further identify the exact effect by grouping them according to A, B, C. Column A: Pro-Myogenesis Column B: Anti-myogenesis A. Pro- proliferation A. Anti- proliferation B. Pro- differentiation B. Anti- differentiation C. Pro- increase in muscle size C. Anti- increase in muscle size EPIMERE/SOMITES Divides into – Sclerotome Development vertebrae development bone development – Dermomyotome Development Myotome Dermatome migrating myoblast D E F E C T I N B O N E / M U S C L E F O R M AT I O N : 1. MECHANISMS OF DEFECTS (2-3 SENTENCES) 2. W H AT I S T H E B I O L O G I C A L E F F E C T ( 2 - 3 SENTENCES) 3. H O W T O A M E L I O R AT E ( 2 - 3 S E N T E N C E S ) 4. REFERENCE LIST