Page 1Page 2Page 3Page 4Page 5Page 6Page 7Page 8Page 9Page 10Page 111Biology 4361Developmental BiologyGilbert Chapter 14. Paraxial and Intermediate MesodermDecember 7, 2006The mesoderm generates all the organs between the ectodermal wall and the endodermal tissuesThe trunk mesoderm of a neurula-stage embryo can be subdivided into four regions: 1. Chordamesoderm- located in the central region - forms notochord 2. Paraxial (somitic) mesoderm- forms the back of the embryo, along the spine- somites - blocks of mesodermal cells on either side of the neural tube- produce connective tissues of the back; bone, muscle, cartilage, dermis 3. Intermediate mesoderm- forms the urogenital system- kidneys, gonads, associated ducts- cortical portion of the adrenal glands 4. Lateral plate mesoderm- forms heart, blood vessels, blood cells- lining of the body cavities- mesodermal components of the limbs (except the muscles - from the paraxial mesoderm)- extraembryonic membranes NOTE - prechordal plate mesoderm lies anterior to the trunk mesoderm- provides the head mesenchyme that forms much of the connective tissue and musculatureof the face - mesodermal subdivisions are specified along a mediolateral (center-to-side) axis by increasingamounts of BMPs- more lateral mesoderm expresses higher BMP4 levels than midline areas- mesodermal identity can be changed by altering BMP4 expression- different BMP concentrations may cause differential expression of the Forkhead (Fox)family of transcription factors- Foxf1 transcribed in lateral plate and extraembryonic mesoderm- Foxc1 and Foxc2 expressed in paraxial mesoderm (somites)PARAXIAL MESODERM: THE SOMITES AND THEIR DERIVATIVESAs the neural tube forms, thick bands of mesodermal tissue extend on either side - referred to as the segmental plate (in chicks) or unsegmented mesoderm (other vertebrates)2 - somites - blocks of paraxial mesoderm cells- specified by BMP-antagonist Noggin - somites contain three major compartments:1. sclerotome - forms vertebrae and rib cartilage2. myotome - forms musculature of the back, ribs, limbs3. dermatome - forms dermis of the back - also, two minor components 4. syndetome - arising within the sclerotome - generates the tendons5. an unnamed group of cell in the posterior somite generates vascular cells of the dorsalaorta and intervertebral blood vessels - note also that the somite cells determine the migration paths for neural crest cells and spinalnerve axonsThe Formation of SomitesThe periodicity of somite formation (Somitogenesis)In the chick, new somites are formed about every 90 minutesMouse - timing more variable - however, somites appear at exactly the same time on both sides - the timing for somite formation is set when the cells first enter the presomitic mesoderm - somite formation depends on “clock and wave” mechanism- oscillating signal (clock) is provided by the Notch and Wnt pathways- rostral-to-caudal gradient provides a moving”wave” of an FGF; sets somite boundaries - direction of somite development (i.e. rostral-to-caudal) is permanent - number of somites is also set at initial stages of presomitic mesoderm formation - important components of somitogenesis: 1. periodicity - temporal formation of new somites- process begins by paraxial mesoderm cells becoming organized into whorls -referred to as somitomeres2. fissure formation (to separate the somites)- somitomeres become compacted; split apart3. epithelialization - outer cells become epithelial4. specification5. differentiationWhere somites form: The Notch pathwayControl of temporal periodicity is not completely understood - Notch signaling pathway involved3 - activating the Notch pathways produces cells which will induce cells anterior to them to formboundaries (incipient somite borders)- somite boundaries are formed at the interface between the Notch-expressing and non-expressing areas - Notch signaling follows a wave-like pattern- Notch gene becomes highly expressed in the posterior region of the forming somite; justanterior to the “cut” - Notch genes are transcribed in a cycle; function as an autonomous “clock” - Notch controls cascade of gene expression that ultimately separates the somites- hairy1 expressed in the presomitic segmental plate in a cyclic, wavelike manner; 90 minperiodicity (in the chick)- caudal domain of the hairy1 expression pattern rises anteriorly; recedes; leaves a band ofexpression that will become the posterior half of the somite- Mesp2 (a transcription factor) gene expression also controlled in cyclic fashion- expressed at the next-forming fission site- ultimately induces EphA4 (an ephrin) - EphA4 produces repulsive interactions that help separate the somitesThe separation of somites from the unsegmented mesodermEph tyrosine kinases and ligand ephrins mediate cell shape changes - critical for somite separation - Eph kinases also cause cell-cell repulsion between the posterior somite and migrating neuralcrest cellsEpithelialization of the somitesCells of new somites are randomly arranged mesenchymal mass - epithelialization comes from synthesis of two cell proteins: - fibronectin (ECM protein)- N-cadherin (adhesion protein) - these rearrange the outer layer of cells into epithelium - ECM proteins may be regulated by Paraxis and Mesp2 (transcription factors)- expressed at the rostral (anterior ) end of the unsegmented mesoderm; region that formssomites- Mesp2 gene controlled by the Notch signaling pathway- Paraxis gene regulated by processes involving the cytoskeleton- cytoskeletal elements are essential for cell shape changes (e.g. mesenchymal-epithelial transition)Somite specification along the anterior-posterior axisSomites will form different structures, depending on original location4 - specification of somites occurs very early in development - segmental plate mesoderm is determined by its position along the anteroposterior axis beforesomitogenesis - somites are specified according to the Hox genes they express- Hox genes are active in the segmental plate mesoderm before it becomes organized intosomites- once established, each somite retains its pattern of Hox gene expression, even iftransplanted into another regionDerivatives of the somitesCells within a somite commit to a fate relatively late, after the somite has already formed - when a somite is first separated form the presomitic