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Basics of Embryology

Embryology is the study of the origin and prenatal development of an organism, comprising the germinal (first two weeks from conception), embryonic (third to eighth week from conception), and fetal period (ninth week from conception until birth). Gestation in embryology refers to conceptional age, i.e., the time period from conception to birth, and should be distinguished from gestational age, an obstetrics term, which is measured in weeks following the first day of the mother's last menstrual period. Primordial cells develop during the embryonic period and migrate to the developing gonads. Further maturation into fertile oocytes and spermatozoa occurs via meiosis during different stages of male and female organism development. Embryonic stem cells are pluripotent and can differentiate into almost any type of tissue, thus being of great interest in the research and development of new therapeutic approaches. For more information on the morphogenesis of organ systems, see the article on embryogenesis.

  • Definition: the study of the origin and prenatal development of an organism.
  • Timing: The periods of embryonic development are measured from the actual point of conception (i.e. conceptional age).
Periods of embryonic development [1]
Period Conceptional age Events
Germinal period 1–2 weeks
  • Fertilization
  • Implantation of the blastocyst in the uterus
  • Amnion formation
Embryonic period 3–8 weeks
  • Differentiation of head, limbs, and torso
  • Organogenesis
  • Highly susceptible to teratogens
Fetal period 9 weeks to birth
  • Growth and differentiation of tissue and organs formed during the embryonic period

Organ system development begins during the embryonic period, while organ maturation occurs during the fetal period!

Primordial germ cell development

  • Occurs during the 4th week of embryonic development
  • Primordial germ cells arise from the yolk sac and migrate to the developing gonads of the urogenital folds.
  • After meiosis, primordial germ cells mature to sex-specific gametes (oocytes and spermatozoa).

Germline

  • Definition: the cells that develop into mature germ cells (gametes), which pass genetic material on to progeny
  • Process: involves meiosis of primordial germ cells within the gonads
    • Oogenesis (development and maturation of the ova): the production of an oocyte with 2–3 polar bodies
    • Spermatogenesis (sperm cell development): production of four functional spermatids

Four functional spermatids or an oocyte with three polar bodies are produced from one primordial germ cell.

All of the oocytes that will ever be produced are formed during the fetal period, whereas sperm production begins at puberty and never stops!

Overview [2][3]

  • Definition: germ cell maturation in which four daughter cells with a recombinant genome are produced from one germ cell
  • Process: Meiosis involves two major phases (referred to as meiosis I and meiosis II) occurring after DNA replication during the S phase of interphase.
    • Meiosis I (equatorial division)
      • Synapsis (syndesis): the pairing of homologous chromosomes
      • Genetic recombination: Individual chromosome segments are exchanged between the maternal and paternal chromatids of homologous chromosomes (recombination) in a process known as crossing over.
      • Chromosome number reduction:
        • A diploid set of chromosomes is divided in half when the homologous chromosomes separate from one another.
        • Disjunction of chromosomes occurs without centromere splitting generating 2 haploid daughter cells, each with 23 chromosome pairs.
    • Meiosis II (nuclear division):
      • Generally corresponds to the phases of mitosis
      • Sister chromatids of each chromosome from the haploid set separate from each other.
      • Disjunction occurs with centromere splitting; each cell entering meiosis II produces 2 daughter cells, each with 23 chromosomes.
  • Result
    • Cell number: 1 mother cell → 4 daughter cells
    • Set of chromosomes: diploid mother cell (2n) → haploid daughter cell (1n)
    • DNA content: 4 chromatids of the mother cell (4C) → 1 chromatid per daughter cell (1C)
    • For sex-specific features, see female reproductive organs and male reproductive organs.

Stages of meiosis I

Stage Number of cells Chromosome set DNA content
Prophase I
  • Leptotene
    • Chromosomes condense and become visible
    • Chromosomes attach to the nuclear envelope
  • Zygotene
    • Synapsis (syndesis): The pairing of homologous chromosomes.
    • Formation of the synaptonemal complex occurs.
  • Pachytene
    • Crossing over: The chromatids crossover (form chiasmata) and exchange genetic material, resulting in genetic recombination of homologous chromosomes.
  • Diplotene
    • The synaptonemal complex disappears.
    • Homologous chromosomes begin to separate, but continue to be held together by the chiasmata (crossover site).
  • Diakinesis
    • The nuclear membrane disintegrates.
    • The spindle apparatus begins to form.
  • 1
  • 2n
  • 4C
Metaphase I
  • Chromosome pairs align at the equatorial plane.
Anaphase I
  • Homologous chromosome pairs separate via the disintegration of the chiasmata.
Telophase I
  • Cell membrane pinches in at the equator, causing the diploid cell to divide into two haploid cells.
  • 2
  • 1n
  • 2C

Stages of meiosis II

Stage Description Number of cells Chromosome set DNA content
Prophase II
  • Chromosomes condense.
  • Formation of the spindle apparatus occurs.
  • 2
  • 1n
  • 2C
Metaphase II
  • Chromosomes align at the equatorial plane.
Anaphase II
  • The two chromatids of each chromosome separate at the centromere.
  • Chromatids migrate to the cell poles.
Telophase II
  • The nuclear envelope reorganizes.
  • Cell membrane pinches in at the equator.
  • The cell divides into two haploid cells, each with one single chromatid.
  • 4
  • 1n
  • 1C
  • Definition: cells capable of differentiating into specialized cells (potency) as well as replicating while maintaining their undifferentiated state (self-renewal)
  • Cell division
    • Symmetric division: Both daughter cells have stem cell properties.
    • Asymmetric division: One daughter cell is a copy of the mother stem cell and the other one is a precursor cell with differentiated properties.
  • Characteristics
    • Totipotency (omnipotency): the ability of a cell to differentiate into all cell types, including extraembryonic (placental) cells
    • Pluripotency: the ability of a cell to differentiate into all cell types, with the exception of extraembryonic cells (for example, the cells of the ectoderm, which can differentiate into nerve or skin cells, but not into other germ layer cells)
    • Multipotency: the ability of a cell to differentiate into more than one related cell type (for example, hematopoietic stem cells, which can differentiate into myeloid or lymphoid cells)
  • Classification
    • Embryonic stem cells (ESCs)
      • Pluripotent cells that can only develop into embryonic cells, but not trophoblastic cells
      • Originate from the inner cell mass during the blastocyte stage
    • Adult stem cells
      • Pluripotent cells that provide a supply of cells for regenerative tissue
      • Originate from differentiated tissues with high replication potency (e.g., bone marrow)

Hematopoietic stem cell transplantation is used to treat hemato-oncologic conditions, e.g., leukemias.

Molecules involved in embryogenesis [4][5][6]
Types of molecules Subgroup/components Function
Transcription factors
  • Homeoboxproteins (Hox proteins)
  • Craniocaudal organization of embryo
  • Positioning of limbs
  • Development and patterning of the skin and limbs
    • Loss-of-function mutations result in misplaced limbs
    • Retinoic acid increases Hox gene expression
  • Pax proteins
  • Differentiation of the paraxial mesoderm
  • Zinc finger proteins
  • Activation or inhibition of genes for growth and differentiation
  • Helix-loop-helix proteins
  • Regulation of muscle development
  • Testis-determining factor (TDF)
  • Development of male gonads
  • Anti-Mullerian hormone expression through induction of the gene SOX-9
Growth factors
  • Transforming growth factor β (TGF-β) superfamily
  • Development of skeletal muscle and the extracellular matrix
  • Epidermal growth factor (EGF) family
  • Differentiation of the nervous system
  • Fibroblast growth factor (FGF) superfamily
  • Produced at the apical ectodermal ridge
  • Regulates development of the limbs by enhancing mitosis of the mesodermal cells
  • Insulin-like growth factor (IGF) family
  • Skeletal and muscle growth
  • Nerve growth factor (NGF) family
  • Neuronal survival and differentiation
  • Hedgehog (e.g., sonic hedgehog gene)
  • Produced at the notochord
  • Is highly expressed at the zones of polarizing activity at the base of limb buds
  • Regulates differentiation of somites along the anteroposterior axis and the neural tube
  • Mutations cause holoprosencephaly (due to failed forebrain cleavage)
  • Wnt (e.g., Wnt-7 gene)
  • Produced at the apical ectodermal ridge
  • Required for organization of body structures along the dorsoventral axis
  • Regulates development of kidneys and limbs and muscle cell differentiation
Cell adhesion molecules
  • Immunoglobulin superfamily (e.g., neural cell adhesion molecule )
  • Binding of a neuron to a neighboring cell
  • Cadherins (Ca2+-dependent transmembrane proteins)
  • Cell-to-cell adhesion (e.g., as a component of desmosomes)
    • Increased expression of E-cadherin, for example, mediates binding between blastomeres.
    • Decreased expression of E-cadherin enables cell migration during embryogenesis.
  • Integrins
  • Binding to the extracellular matrix
  • Involved in cell migration, cell division, cell differentiation, etc.
Intercellular channels
  • Gap junctions (nexus)
  • Communication between neighboring cells
  • Facilitation of signaling molecules (e.g., retinoic acid) channel crossing to regulate gene activity.
Extracellular matrix
  • Collagen
  • Glycosaminoglycans
  • Proteoglycans
  • Glycoproteins
  • Binding, transportation, and distribution of signaling molecules
Relevant hormones involved in embryogenesis
  • Androgens (testosterone )
  • Differentiation of sexual organs
  • Thyroxine
  • Transcription modulation of various genes through intracellular receptors, e.g., those for CNS development

The FGF gene triggers the Fetal Growth of Fingers.

Cellular developmental processes [4]
Process Description Examples of the process Examples of associated pathology
Apoptosis Programmed cell death Fragmentation and, thus, the separation of the webbed embryonic fingers and toes Syndactyly
Differentiation The process by which primitive (e.g., stem cells) become specialized cells Spermatogenesis and oogenesis Infertility
Fusion Joining of two or more cells, epithelium, or tissue Linea alba (abdominal wall) is formed by by fusion of the aponeurosis of abdominal muscles Gastroschisis
Membrane of the oocyte fuses with a spermatozoid during fertilization Infertility
Medial facial prominences are fused to form the midline of the nose and philtrum of the upper lip Cleft lip
Anterior ⅔ and posterior ⅓ of the tongue N/A
Urethral folds of the penis Hypospadias
Heart septae are formed by fusion of endocardial cushions Endocardial cushion defects, e.g., persistent foramen ovale
Migration Movement of the cells to a specific destination Neural crest cells along the gastrointestinal tract Hirschsprung disease
Neural crest cells to the heart Conotruncal cardiac abnormalities
Primordial germ cell from the yolk sac to the undifferentiated gonads Differences (disorders) of sex development
Neuronal cells during fetal brain development Lissencephaly: underdevelopment of cerebral grooves and folds
Proliferation Increase in the number of cells (mediated by cell division) Gastrulation Conjoined twins