Paraxial & Intermediate Mesoderm


Mesoderm of the Neurula Stage

     1. Chordamesoderm - forms the notochord

     2. Paraxial Mesoderm (somitic dorsal mesoderm) - here dorsal refers to structures that will form  in the back of the embryo along the spine

   Cells will form somites - blocks of mesoderm cells on both sides of the neural tube - produce connective tissues of the back (bone, muscle cartilage and dermis)

     3. Intermediate mesoderm - forms the urogenital system

Mesoderm of the Neurula Stage

    4. Lateral late mesoderm- forms the heart, blood vessels & blood cells - the lining of the body cavities - and also all mesodermal components of the limb except the muscles

  Also forms extraembryonic membranes important in transporting nutrients to the embryo

    5. Head mesenchyme - forms connective tissues and musculature of the face

Lineages of Mesoderm






Paraxial Mesoderm

     Mesodermal cell formation occurs synchronously with neural tube formation

     Thick bands of mesodermal cells form on either side of the neural tube

   This is paraxial mesoderm - referred to as segmental plate in birds and unsegmented mesoderm in mammals

     As the primitive streak regresses & neural folds begin to gather at the center of the embryo - the paraxial mesoderm divides into block


Somites: Overview

     Somites are transient - but important in organizing the segmental pattern of vertebrate embryos

     Important in migration paths for neural crest cells and spinal nerve axons

     Give rise to the cells that form the vertebrae and ribs, dermis of the dorsal skin, skeletal muscle of the back and the skeletal muscle of the body wall and limbs

Gastrulation - Neurulation in the Chick







Periodicity - Somite Formation

     First somites - anterior portion of the trunk - new somites bud off from the rostral end of the paraxial mesoderm at regular intervals

     Somite formation begins as cells become organized into whorls of cells - somitomeres

   Somitomeres become compacted - bond together by a epithelium & will separate off as a individual somite

     Somite number is a good indicator of how far along an embryo is in development

   50 in chicks, 65 in m ice and 500 in snakes

Neural Tube and Somites







Hairy Gene and Somite Formation

     First expressed in the caudal portion of each somite

     Second - it is expressed in the presomitic segmental plate or unsegmented mesoderm in a cyclic wavelike manner cresting every 90 minutes

   Starts caudally moves anteriorly as the somite forms

   Caudalmost region of this anterior expression band correlates with the posterior terminus of the next somite to be formed

Separation - Somite Formation

    Hairy gene encodes a transcription factor - target unknown

    One possible set of targets - genes for ephrin  and its receptor

  Remember ephrin ligands cause repulsion between the migrating neural crest cells and the posterior somite

  Ephrin may be critical for somite separation

Epithelialization - Somite Formation

     Conversion from mesenchyme tissue into an epithelial block occurs even before each somite splits off

     Fibronectin and N-cadherin links these cells into  an arrays that will form tight junctions - and generate their own basal laminae

     These extracellular proteins  are likely regulated by the expression of the Paraxis gene

Specification and Commitment of Somitic Cell Types

    Axial specification - although somites look identical they will form different structures at different positions along the anterior to posterior axis

  Hox gene involved in this specification

Specification and Commitment of Somitic Cell Types

     Differentiation within  the somite

   Sclerotome - mesenchymal cells - forms vertebral cartilage - in the thorax also form the ribs

   Dermamyotome - muscle forming region

   Epaxial muscles - closest to the neural tube (deep muscles of the back)

   Hypaxial muscles - body wall, limb and tongue musculature

   Dermatome - central region of the demamyotome - form the mesenchymal connective tissue of the back skin (dermis)

   Also forms the distal cartilage of the ribs & most ventral portion of the ribs

Trunk Area - 2 and 3 Day Embryos





Trunk Area  - 4  and Late 4 Day Embryos









Specification of Somitic Regions

    Specification by paracrine factors secreted by neighboring tissue

    The sclerotome specified by sonic hedgehog protein from the notochord and floor plate cells

    The dermatome is specified by neurotrophin-3 - secreted by the roof plate cells of the neural tube

Specification of Somitic Regions

    The two myotome regions specified by different factors

    The epaxial myotome is specified by Wnt proteins from the dorsal neural tube

    The hypaxial myotome is specified by BMP4 (others?) from the lateral plate mesoderm

Patterning of the Somite










    Myogenic bHLH family of transcription factors are induce in the cells that will be come muscles (myoblasts)

    These cells align themselves & fuse into myotubes characteristic of muscle tissue

  Thus the multinucleate myotubes are the products of several myoblasts joining together & dissolving cells membranes between themselves

Conversion of Myoblasts Into Muscles








Skeletal Lineages

     Three distinct lineages that generate the skeleton

     Somites generate the axial skeleton

     Lateral Plate mesoderm generates the limb skeleton

     Cranial neural crest gives rise to the brachial arch (gill apparatus in fish & jaws and ears in mammals)and craniofacial bones and cartilage


    Intramembranous ossification - direct conversion of mesenchymal tissue into bone

  Occurs primarily in the bones of the skull & turtle shells

    Endochondral ossification - mesenchymal cells differentiate into cartilage - then the cartilage is replaced by bone

Intramembranous Ossification

     Neural crest derived mesenchymal cells proliferate and condense into compact nodules

     Some of the cells develop into osteoblasts - committed bone precursor cells

     These cells secrete a collagen-proteoglycan matrix that is able to bind calcium salts

     Osteoblasts that get caught in the calcified matrix  become osteocytes - bone cells

     Eventually a compact mesenchymal cell layer forms around the region of calcification - called the periosteum

Intramembranous Ossification








Endochondral Ossification

    1. Mesenchymal cells are committed to become cartilage cells

    2. Committed mesenchymal cells condense into compact nodules & differentiate into chrondocytes

    3. Chrondrocytes proliferate rapidly to from the model for the bone

Endochondral Ossification

     4. Chrondrocytes stop dividing & increase their volume dramatically

   Hypertrophic chrondrocytes - alter matrix to enable it to become mineralized by calcium carbonate

     5. Invasion of the cartilage model by blood vessels - hypertrophic chrondrocytes die - spaces become bone marrow

   Group of cells surrounding the cartilage model differentiate into osteoblasts

   They begin to form bone on the partially degraded cartilage

Endochondral Ossification








Epiphyseal Growth Plates

     Long bones - ossification spreads outward in both directions

     As the endochondral ossification front nears the ends of the cartilage model - chrondrocytes proliferate prior to undergoing hypertrophy - pushing out the cartilage ends of the bone

     This is the epiphyseal growth plate - three regions

   1. Region of chrondrocyte proliferation

   2. Region of mature chrondrocytes

   3. Region of hypertrophic chrondrocytes

Epiphyseal Growth Plates










     Multinucleate cells that enter the bone through blood vessels

     These cells pump out hydrogen ions into the surround area and acidifying and solubilizing it

     These cells continually remodel bone throughout adult life

     Osteoblasts lay down new bone to undue the damage caused by osteoclasts

Intermediate Mesoderm - Progression of Kidney Types

    Pronephric duct (day 22 in humans; day 8 in mice)- arises in the intermediate mesoderm just ventral to the anterior somites

   The cells of the duct migrate caudally - anterior region of the duct induces the adjacent mesenchyme to form tubules of the initial kidney - the pronephros

   Form functional kidneys in fish and amphibian larvae

Intermediate Mesoderm - Progression of Kidney Types

    In mammals - anterior portion of the pronephric duct degenerates - more caudal portions persist - serve as central component of the excretory system throughout development

   called the nephric or Wolffian duct

Intermediate Mesoderm - Progression of Kidney Types

     As the pronephric tubules degenerate -  the middle of the duct induces a new set of kidney tubules to from - mesonephros

    In humans and mice it never functions in urine formation

    However it is the source of hematopoietic stem cells necessary for  blood cell formation

    In male mammals some of these tubules become sperm carrying tubes - the vas deferens & efferent ducts

Intermediate Mesoderm - Progression of Kidney Types

     Permanent kidney of amniotes - metanephros

     Metanephrogenic mesenchyme forms in posteriorly located region of intermediate mesoderm

    It induces formation of a branch from each of the paired nephric ducts

   Called ureteric buds - separate from the nephric duct to become the ureters

   As they pass through the metanephrogenic mesenchyme - induces formation nephrons

   Called reciprocal induction - ureteric bud & metanephrogenic mesenchyme form the kidney
   8 sets of signals appear to be involved

Reciprocal Induction- Kidney Development