Paraxial Mesoderm and Somites Overview

Paraxial Mesoderm: Somites and Their Derivatives

• Segmentation is a highly conserved feature in vertebrates, crucial for the evolution of specialized functions.
• Vertebrate species have similar segment numbers, but segment size and function vary based on environmental needs.
• Thoracic segments are unique in having ribs which protect organs, and their number varies greatly among species.
• Segment number/size is determined by mesodermal division along the anterior-posterior axis; snakes have ~300 segments while humans have ~38.
• Mesoderm forms between the endoderm and ectoderm synchronously with neural tube development.
• Presomitic mesoderm (PSM) forms somites, vital for structuring vertebrae, muscle, and skeleton.

Major Mesoderm Lineages

• Chordamesoderm (axial mesoderm): Forms the notocord and intervertebral discs.
• Paraxial mesoderm (somitic mesoderm): Forms somites and head mesoderm; somites are transitory epithelial blocks of cells near the neural tube, and differentiate into muscle and connective tissues of the back, as well as face and skull tissues.
• Intermediate mesoderm: Forms the urogenital system (kidneys, gonads, and ducts).
• Lateral plate mesoderm: Forms circulatory system, body cavity linings, pelvic/limb bones, and extra-embryonic membranes.

Gastrulation and Neurulation (Chick Embryo, Mesodermal Perspective)

• Mesoderm formation during gastrulation occurs between the endoderm and ectoderm.
• Sequential stages show the formation of a notochord, paraxial mesoderm, and lateral plate mesoderm.
• Somite formation and other mesodermal development processes are shown in detail.
• Stages are depicted (Embryonic day 24-48).

Specification of Somites

• Mesodermal subtypes (chordamesoderm, paraxial, intermediate, and lateral plate) development is specified along the mediolateral axis due to varying BMPs level, with higher BMP4 expression in more lateral cells.
• Noggin (BMP inhibitor) helps shape the BMP gradient. Adding Noggin to lateral plate mesoderm reshapes it into paraxial mesoderm.
• Hox genes on chromosomes are patterned to reflect their expression along the antero-posterior axis; Hox gene expression determines somite identity and specification.

Somitogenesis

• Somitogenesis progresses from head to tail direction.
• Presomitic mesoderm forms somitomeres (cell groups, precursors to somites).
• Epithelial boundaries define each somite.
• Somite counts vary across species (humans: 38-45; mice: 65; snakes: >500).

Eph-Ephrine Signaling & Somite Formation

• Somites transition from mesenchymal to epithelial cells (MET) through cell conversion.
• Mesodermal posterior (Mesp) transcription factors initiate MET, but they are restricted to anterior somite halves.
• Eph-ephrin signaling regulates epithelialization, leading to distinct somite boundaries.
• Boundary formation involves Cdc42 repression and integrin x5-fibronectin interactions for fissure formation/separation.

Notch Delta Signaling in Somitogenesis

• Loss of Notch target Lunatic Fringe (Lfng) or its partner Distal-less-3 (Dll3) in mice causes severe vertebral malformations.
• Similar vertebral defects are observed in humans with Lunatic Fringe gene mutations.
• This highlights conserved roles in vertebral segmentation across different species.

How Many Somites Does a Snake Have?

• Corn snake embryos at different stages show increasing somite formation.
• Corn snakes have a threefold more oscillation of Lunatic fringe expression than mice at similar stages.
• Four vertebrate species exhibit distinct somite formation patterns.

Regulatory Mechanisms Governing Somitogenesis

• Segmentation clock involves Notch-Delta signaling and the timing/order of Hox gene expression.
• Hox genes repress Wnt signaling and indirectly affect Fgf8 expression, which influences segmentation.
• Retinoic acid inhibits posterior signals (Fgf8, Wnt3a), promoting anterior somite formation.
• Fgf8 feedback represses retinoic acid through Cyp26A1 while maintaining posterior growth.
• Signaling balances (retinoic acid, Wnt, and Fgf8) establish a determining front, for anterior somite formation before posterior.

Sclerotome Development

• Sclerotome progenitors express Pax1.
• They transition from epithelial to mesenchymal cells (EMT)
• Migrate towards the neural tube.

Syndetome Development

• Forms tendons; portion of sclerotome.
• Expresses Scleraxis gene.
• Functions to connect muscle and bone.
• Located in the most dorsal segment of the sclerotome.

Induction of Scleraxis

• FGF from the myotome signals the most dorsal sclerotome cells to differentiate as syndetomes.
• Syndetome cells migrate and differentiate into tendons.

Primaxial and Abaxial Domains of Vertebrate Mesoderm

• Lateral Somitic Frontier separates primaxial and abaxial muscles (somite derived vs lateral plate dermis).
• Satellite cells- undifferentiated myoblasts, stay around mature muscles, as skeletal muscle stem cells, crucial for growth and repair.
• Day-9/13 chick embryo's mesoderm displays Prox1 gene expression in the abaxial region, showcasing the lateral somitic frontier dividing regions.

Differential Gene Expression in Myotome

• Primaxial myotome development is driven by Wnt1/Wnt3a (dorsal neural tube) and low Shh.
• Pax3 and Wnt expression is key for myogenin and MRF4 activation, leading to muscle formation.
• BMP4 inhibition by Noggin allows Wnt from the epidermis to induce abaxial myotome formation.

Ablating Noggin-Secreting Epiblast Cells

• Control Embryos have normal muscle formation with strong myosin presence.
• Noggin-ablated embryos display significant muscle loss, eye defects and abdominal wall herniation.

This quiz explores the characteristics and functions of paraxial mesoderm and somites in vertebrate development. Understand the significance of segmentation and how mesodermal differentiation influences the structure of vertebrae, muscles, and skeletons. Test your knowledge about the evolution and variance of somite structures across different species.