Developmental Biology Lesson 24 (BIOL 346) PDF

BIOL 346 Developmental Biology Lesson 24 Chapter 19: Paraxial Mesoderm: The Somites and Their Derivatives  Segmentation of the body plan is a highly conserved feature Conserved Segmentation: Segmentation is a fundamental feature in vertebrat...

BIOL 346 Developmental Biology Lesson 24 Chapter 19: Paraxial Mesoderm: The Somites and Their Derivatives  Segmentation of the body plan is a highly conserved feature Conserved Segmentation: Segmentation is a fundamental feature in vertebrates, supporting the evolution of specialized functions. Species-Specific Variation: Vertebrate species share similar segment numbers (e.g., cervical vertebrae in humans and giraffes), but segment size and function vary to meet environmental needs Thoracic Vertebrae: Thoracic segments are unique in having ribs, which protect organs. The number of these segments varies widely between species (e.g., humans, mice, and snakes). Determining Segment Number: Segment size and number are defined by mesodermal division along the anterior-posterior axis (e.g., ~300 segments in snakes vs. ~38 in humans). Mesoderm Formation During Gastrulation: Mesoderm forms between the endoderm and ectoderm in sync with neural tube development. Somite Formation: Cells from the presomitic mesoderm (PSM) create somites, essential for organizing vertebrae, muscle, and skeletal structure. Fig. 19.1: The development of the major mesodermal lineages is diagrammed in this schematic of a section through the non-limb somitic region of an amniote embryo Major mesoderm lineages Chordamesoderm (aka axial mesoderm) Gives rise to notochord & intervertebral discs Paraxial mesoderm (aka somitic mesoderm) Gives rise to somites & head mesoderm Somite: transitory epithelial blocks of cells positioned adjacent to neural tube Somites ➔ muscles and connective tissues of back (including dermis, muscle, and skeletal components) Head mesoderm (anteriormost paraxial mesoderm) ➔ skeleton, muscles, connective tissue of face & skull Intermediate Mesoderm Gives rise to urogenital system (kidneys, gonads, and their ducts) Lateral Plate Mesoderm Gives rise to circulatory system, body cavity linings, pelvic and limb bones, extra- embryonic membranes Fig.19.2: Gastrulation and neurulation in the chick embryo, focusing on the mesodermal component (A–C) show 24-hour embryos, (D–F) show 48-hour embryos. Fig. 19.3: (A) Staining for the medial mesodermal compartments in the trunk of a 12-somite chick embryo and (B) specification of somites Mesodermal subtypes (chordamesoderm, paraxial, intermediate, and lateral plate) are specified along the mediolateral axis by varying levels of BMPs, with higher BMP4 expression in more lateral mesodermal cells. Noggin, a BMP inhibitor, helps shape the BMP gradient; adding Noggin to lateral plate mesoderm re-specifies it into somite-forming paraxial mesoderm. (A) Stains: Chordin (blue) in notochord, Paraxis (green) in somites, Pax2 (red) in intermediate mesoderm. (B) Noggin induces somite formation, marked in re- specified area (bracketed). Fig. 19.7: Anterior-posterior specification of the somites Each somite differentiates into specific structures along the anterior-posterior (A-P) axis. Hox gene expression determines the identity and specification of each somite. Hox genes are organized on the chromosome in a pattern that reflects their expression along the A-P axis. Somite fate can be modified through presomitic mesoderm (PSM) grafting or by altering Hox gene expression.  Somitogenesis Somitogenesis progresses in a head-to-tail direction. Presomitic mesoderm → somitomere (cell group, precursor to somites). Epithelial boundaries define each somite. Somite count varies by species: Zebrafish: 33 Humans: 38-45 Mice: 65 Snakes: up to 500 Fig. 19.9: SEM of neural tube and somites in the chick embryo Fig. 19.11: Eph-ephrin signaling regulates epithelialization during somite boundary formation Somites form through a mesenchymal-to-epithelia transition (MET) as mesenchymal cells convert to epithelial cells. Mesodermal posterior (Mesp) transcription factor initiates MET, becoming restricted to the anterior half of each forming somite. Mesp upregulates Eph A4 in the anterior somite half, while Eph A4 induces ephrin B2 expression in the adjacent posterior half. Eph-ephrin signaling fosters epithelialization, forming distinct somite boundaries. This boundary formation involves Cdc42 repression and integrin α5-fibronectin interaction for fissure formation. Fig. 19.16: Notch-Delta signaling is essential for proper somitogenesis (A) In mice, loss of Notch target Lunatic fringe (Lfng) or its partner Distal- less-3 (Dll3) leads to severe vertebral malformations. (B) Similar vertebral defects are observed in humans with mutations in the LUNATIC FRINGE gene, highlighting conserved roles in vertebral segmentation across species. Fig. 19.18: How many somites does a snake have? (A) Somite count in snakes: Corn snake embryos at different stages show increased somite formation. (B) Lunatic fringe Oscillations: Corn snakes have threefold more oscillations of Lunatic fringe expression in the PSM compared with mice embryos at similar stages. (C) Vertebrate Somite Pattern: Four vertebrates exhibit distinct somite formation patterns. Fig. 19.19: Model of the regulatory mechanisms governing somitogenesis __Segmentation Clock: Notch-Delta signaling regulates the timing and order of Hox gene expression. Hox Gene Function: Hox genes repress Wnt signaling and, indirectly, Fgf8 expression, impacting the segmentation process. Anterior-Posterior Patterning: Retinoic Acid: Inhibits posterior signals (Fgf8 and Wnt3a), promoting anterior somite formation. Fgf8 feedback: Represses retinoic acid via Cyp26A1, maintaining posterior growth. Signaling Balance: Interaction between retinoic acid, Wnt, and Fgf8 establishes a determination front, enabling anterior somites to form before posterior somites.  Sclerotome Development Sclerotome Progenitors: Express Pax1 Undergo an epithelial to mesenchymal transition (EMT) Migrate towards the neural tube Fig. 19.20: Transverse sections through the trunk of the day 2–4 chick embryo Fig. 19.21: Major postulated interactions in the patterning of the somite Signaling Centers Influencing Somite Patterning Notochord and Floor Plate: _Secrete Shh and Noggin_ Neural Tube: Secretes Wants and BMPs_ Fig. 19.22: Re-segmentation of the sclerotome to form vertebrae __PDGF and Epimorphin: Attract sclerotome cells to surround the neural tube and notochord Resegmentation: Splitting of sclerotome into anterior and posterior halves After myotome enervation, anterior and posterior portions of adjacent sclerotome segments fuse _Resegmented sclerotome gives rise to the vertebrae Fig. 19.24: Scleraxis is expressed in the progenitors of the tendons Syndetome Development Portion of sclerotome that forms tendons Cells express the Scleraxis gene Tendons function to connect muscle and bone Located in the most dorsal portion of the sclerotome Fig. 19.25: induction of Scleraxis in the chick sclerotome by Fgf8 from the myotome FGF from Myotome signals the most dorsal cells of sclerotome to become syndetome Syndetome cells migrate and then differentiate into tendons Fig. 19.26: Primaxial and abaxial domains of vertebrate mesoderm Lateral Somitic Frontier: Boundary between primaxial and abaxial muscles; somite-derived vs. lateral plate-derived dermis. Satellite cells: Undifferentiated myoblasts remain around mature muscles as skeletal muscle stem cells for growth and repair. (A) Shows mesoderm differentiation (red) in an early chick embryo. (B) Day-9 chick embryo displays Prox1 gene expression (dark stain) in the abaxial region, with the lateral somitic frontier (dotted line) marking the boundary. (C) Regionalization of mesoderm in a day-13 chick embryo, highlighting distinct mesodermal compartments. Fig. 19.27: Differential gene expression in myotome Primaxial Myotome Driven by Wnt1/Wnt3a (dorsal neural tube) and low Shh. Pax3 enables Myf5 expression, leading to myogenin and MRF4 activation for muscle formation. Abaxial Myotome BMP4 inhibition by Noggin allows Wnt from the epidermis to induce abaxial myotome. Fig. 19.28: Ablating Noggin-secreting epiblast cells results in severe muscle defects Control Embryo: Normal muscle formation with strong myosin presence. Noggin-Ablated Embryo: Significant muscle loss, eye defects, abdominal wall herniation.