Embryology

Embryonic and Fetal Development

• Embryo: Development during the first 8 weeks after fertilization.

• Fetus: Development from week 8 to birth.

Fertilization and Early Cell Division

1. Zygote Formation:

   • A fertilized egg becomes a zygote.

   • The zygote undergoes mitosis, producing a cluster of 8-16 cells called the morula.

   • The morula is a solid mass of undifferentiated cells.

   • Each cell in the morula can become any tissue of the embryo or placenta (totipotent).

2. Entry into Uterus:

   • The morula typically enters the uterus at this stage.

Blastocyst Formation

• Transition from Morula to Blastocyst:

  • Around day 5, the morula begins to cavitate (form a cavity).

  • The structure is now called a blastocyst, which has:

    • Blastocyst cavity (blastocoel).

    • Trophoblast: Outer cell layer.

    • Inner cell mass (embryoblast): Located at one pole of the embryo.

Implantation

1. Trophoblast Differentiation:

   • The trophoblast differentiates into:

     • Cytotrophoblast: Cellular layer.

     • Syncytiotrophoblast: Invades the uterine wall and secretes human chorionic gonadotropin (hCG).

2. Role of hCG:

   • Maintains the corpus luteum for approximately 2 months.

   • The corpus luteum produces progesterone, supporting the uterine lining and preventing menstruation.

   • By the end of 2 months, the placenta takes over progesterone production.

Formation of the Bilaminar Embryo

• Inner Cell Mass Differentiation:

  • The inner cell mass forms two layers:

    • Epiblast: Dorsal layer.

    • Endoderm (hypoblast): Ventral layer.

• Amniotic Cavity:

  • Forms dorsal to the epiblast.

• Prochordal Plate:

  • Endoderm cells at one pole of the embryo differentiate to form the prochordal plate, marking the cranial end of the embryo.

• Blighted Ovum

  • Trophoblast is maintained but inner cell mass fails to develop

  • results in hCG production without pregnancy

Gastrulation: Formation of Trilaminar Embryo

1. Primitive Streak Formation:

   • Epiblast cells at the caudal end differentiate and form the primitive streak and groove. Daughter cells of the primitive streak becomes the mesoderm.

   • The streak extends cranially, making the Primitive Knot. Daughter cells of the Primitive Knot become the notochord.

2. Three Germ Layers:

   • Epiblast cells migrate through the primitive streak to form:

     • Ectoderm: Remaining epiblast cells.

     • Mesoderm: Migrating cells that form a layer between ectoderm and endoderm.

     • Endoderm: Ventral layer of the bilaminar disc.

3. Notochord Formation:

   • Cells from the primitive knot migrate cranially in a single-file line to form the notochord.

     • Migration ends at the prochordal plate

   • The notochord induces the ectoderm to differentiate into neuroectoderm by producing potent growth factors.

     • ectoderm cells that do not differentiate become the Surface Ectoderm.

Neurolation: Neural Tube Formation

• Neural Plate and Groove:

  • The ectoderm above the notochord thickens to form the neural plate.

  • The plate folds to form the neural groove.

• Neural Tube:

  • The neural groove deepens and fuses dorsally to form the neural tube.

  • Closure begins mid-embryo and progresses cranially and caudally (like a zipper).

  • Closure completes:

    • Cranial neuropore: Day 26.

    • Caudal neuropore: Day 28.

• Neural Crest Cells:

  • Some neuroectoderm cells at the crest of the groove separate to form neural crest cells, which migrate to form:

    • Peripheral nervous system (ganglia, Schwann cells).

    • Other structures (melanocytes, adrenal medulla).

• Neuroectoderm

  • Neural tube differentiates into the CNS

  • Neural Crest differentiates into the PNS

Failure of Neural Tube Closure

• Low folic acid is linked to neural tube defects:

  • Spina bifida (incomplete closure of the spinal region):

    • Occulta.

    • Manifesta (meningocele, meningomyelocele).

  • Anencephaly: Failure of cranial closure, typically incompatible with life.

Somites and Mesoderm Differentiation

1. Somite Formation:

   • Paraxial mesoderm segments into paired structures called somites.

   • Somites are arranged along the neural tube and differentiate into:

     • Sclerotome: Forms bones (e.g., vertebrae).

     • Myotome: Forms skeletal muscles.

     • Dermatome: Forms dermis of the skin.

2. Somite differentiation

   • Cell bodies from ventral neural tube connects to myotome (multipolar)

   • Neural Crest connects to Dermatome and Dorsal neural tube (unipolar)

3. Somite Innervation:

   • Each somite is innervated by a spinal nerve, maintaining this pattern after birth.

   • Example: A spinal nerve innervates all tissues derived from its somite.

   • motor fibers cell bodies are located in Ventral aspect of spinal cord

   • sensory fiber cell bodies are located in Dorsal Root Ganglion which lies dorsolateral to spinal cord.

4. Spinal Nerve Damage

   • result in sensation and tone

   • paresis: loss of power

   • hypesthesia: decreased sensation

   • Paresthesia: pins and needles

   • flaccid paralysis: damage to muscle nerve

     • undergoes atrophy quickly

   • spastic paralysis: damage to cortical nerve

5. Occipital somites

   • hook up to the brain stem

   • only form myotomes (motor only)

6. Pre-Otic Somites

   • 1st (oculomotor) and 2nd (trochlear) hook up to the mesencephalon (mid brain), 3rd (abducnes) hooks up to the pons

   • only give rise to skeletal muscles (extraocular muscles)

   • 3rd nerve (oculomotor) also have parasympathetic innervation

     • parasympathetic fibers grows outside of the sympathetic fibers

     • Perception of oculomotor muscles are done by Outflow theory. the brain perceives space of eyes by signals sent out.

Branchial Arches

1. Formation:

   • Five arches (1st, 2nd, 3rd, 4th, 6th) form on the anterolateral surface of the embryo.

   • Each arch is associated with an aortic arch and specific cranial nerves.

2. Innervation:

   • 1st Arch: Trigeminal (V).

     • cranial arch: maxillary arch (sensory)

     • Caudal arch: mandibular arch (sensory + motor)

     • Opthalmic branch (sensory)

   • 2nd Arch: Facial (VII).

   • 3rd Arch: Glossopharyngeal (IX).

   • 4th Arch: Vagus (X).

   • 6th Arch: Spinal Accessory (XI).

     • protected by cervical spinal nerve

3. Pretrematic nerve: Every nerve sends a nerve one cranial nerve cranial to it.

4. Development of the face:

   • Frontal nasal process (head mesenchyme) moves down to meet with the lateral nasal process (maxillary mesenchyme)

5. Derivatives:

   • Muscles and skeletal structures arise from each arch. For example:

     • 1st Arch: Muscles of mastication, maxilla, mandible.

     • 2nd Arch: Muscles of facial expression, hyoid.

6. Sensory innervation to head

7. Body of tongue: Lingual of V3

   • skin of the body of the tongue come from V3

   • taste comes from pretrematic arch CNVII (chorda tympani)

8. Muscles of V3 Innervation

   • Mastication:

   • Tensor muscles:

   • Muscles of floor of mouth:

9. Second arch: Facial Nerve

   • SVE: innervates skeletal muscles of facial expression (BONE TO SKIN)

   • GSA: skin of ear canal

     • Ramsay Hunt: Herpes Zoster Oticus (vesicular reaction of ear canal)

       • Similar to Bell palsy but not self limiting

       • Leads to swelling of ganglia in the ear compressing motor fibers in the ear.

   • SVA: taste buds of tongue

   • GVE: autonomic (CN therefore only parasympathetic)

     • Lacrimal Gland.

10. Third Arch: Glossopharyngeal

    • SVE: stylopharyngeus muscle

    • GSA (touch) and SVA (taste): sensory and taste for the root of the tongue

      • Leads to a gag reflex

    • GVE: Autonomic- parasympathetic to parotid gland

    • GVA: innervates carotid body (BP and pO2) and sinus

11. Fourth Arch: Vagus nerve

    • SVE: pharyngeal constrictors and soft muscles

    • GVE: autonomic to GI

    • GVA: Sensory from Internal organs

    • SVA: Taste buds of pharynx

    • GSA: Touch to ear canal

    • Muscles of Palate

      • Palatoglossus

      • Palatophyngeus

      • Levator palatine

      • Musculus Uvulae

12. sixth Arch: Spinal accessory

    • SVE ONLY

      • Trapezius

      • Sternocleidomastoid

    • Receives pretrematic branch from cervical spinal cord (goes through foramen magnum and exits through the jugular)

    • Torticollis: Damage and contraction of the SCM

      • superior oblique palsy:

        • tilting shoulders to compensate for palsy of EOM.

        • Differential: cool, superior oblique palsy, SCM contraction

Key Neural and Muscular Development

1. Cranial Somites:

   • Four occipital somites and three pre-otic somites contribute to head and neck muscles.

   • Pre-otic somites give rise to extraocular muscles (innervated by III, IV, VI).