Major Developmental Processes

Human development proceeds through a defined, ordered sequence of processes, each building directly and mechanistically on the product of the one before it. Understanding development means understanding each of these processes individually, and understanding that none of them can occur out of sequence.

Gametogenesis is the production of haploid gametes, spermatozoa in the male and oocytes in the female, from diploid germ cell precursors through the specialised cell division process of meiosis.

Meiosis consists of two sequential divisions. Meiosis I is a reductional division, separating homologous chromosome pairs and halving the chromosome number from diploid to haploid; it is preceded by crossing over between homologous chromosomes during prophase I, which generates genetic recombination and is the principal source of genetic diversity between siblings. Meiosis II is an equational division, mechanically similar to mitosis, separating sister chromatids.

Spermatogenesis occurs continuously from puberty onward within the seminiferous tubules of the testis, and a full cycle from spermatogonium to mature spermatozoon takes approximately 64 to 74 days. Spermatogenesis produces four equal, functional haploid spermatozoa from each primary spermatocyte.

Oogenesis begins prenatally, with all primary oocytes arrested in prophase I of meiosis I before birth, and remains arrested until that individual oocyte is recruited for ovulation, potentially decades later.

Meiosis I completes only just before ovulation, producing a secondary oocyte and a small, nonfunctional first polar body, and meiosis II arrests again at metaphase II, completing only if fertilisation occurs.

Oogenesis therefore produces only one functional gamete per completed meiotic sequence, with the surplus genetic material discarded into polar bodies.

Fertilisation is the fusion of spermatozoon and secondary oocyte, occurring in the ampulla of the uterine tube, typically within 24 hours of ovulation.

Fertilisation proceeds in these steps.

Sperm penetration of the corona radiata and zona pellucida, triggering the acrosome reaction: release of enzymes from the sperm acrosomal cap that digest a path through the zona pellucida.
Fusion of the sperm and oocyte plasma membranes.
Completion of the oocyte's second meiotic division.
Fusion of the male and female pronuclei to restore the diploid chromosome number and form the zygote.

Fertilisation triggers the cortical reaction, release of cortical granule contents from the oocyte that alter the zona pellucida to prevent entry of additional spermatozoa, a mechanism preventing polyspermy, fertilisation by more than one sperm, which would produce a nonviable, chromosomally abnormal conceptus.

Cleavage is a series of rapid mitotic divisions of the zygote occurring without an accompanying increase in overall size, since each division simply partitions the existing cytoplasm into progressively smaller and more numerous cells, blastomeres.

Cleavage begins around 24 to 30 hours after fertilisation and proceeds through the 2-cell, 4-cell, and 8-cell stages over the following two to three days. Around day 3, compaction occurs, in which the blastomeres tighten their intercellular junctions and flatten against one another, maximising cell-to-cell contact and forming the morula, a solid ball of approximately 12 to 16 cells.

By day 4 to 5, fluid begins to accumulate between the inner cells of the morula, forming a fluid-filled cavity, the blastocoele, and converting the morula into a blastocyst.

The blastocyst contains two distinct cell populations established at this stage.

The inner cell mass, a cluster of cells that will give rise to the embryo proper.
The trophoblast, the outer epithelial layer surrounding the blastocoele, which will give rise to the placenta and fetal membranes.

Implantation is the process by which the blastocyst embeds into the uterine endometrium, establishing the physical and physiological connection between the conceptus and the mother.

The blastocyst first sheds the zona pellucida, hatching, around day 6, permitting direct contact between the trophoblast and the endometrial epithelium. Apposition and attachment follow, with the blastocyst orienting so that the embryonic pole, the pole overlying the inner cell mass, contacts the endometrium first.

The trophoblast then invades the endometrial stroma, differentiating into an inner, mononuclear cytotrophoblast and an outer, multinucleated syncytiotrophoblast, with the syncytiotrophoblast doing the active invading. Implantation is normally complete, with the blastocyst fully embedded within the endometrium, by around day 9 to 10.

Gastrulation is the process that converts the two-layered bilaminar embryonic disc into a three-layered trilaminar disc, establishing the three definitive germ layers, ectoderm, mesoderm, and endoderm, from which every tissue of the body will subsequently derive.

Gastrulation begins around day 14 with the appearance of the primitive streak, a linear thickening of the epiblast at the future caudal end of the embryo, which defines the cranial to caudal axis and the midline of the embryo for the first time.

Epiblast cells migrate toward and through the primitive streak, a process called ingression, and disperse to displace the hypoblast, forming definitive endoderm, and to occupy the space between epiblast and endoderm, forming intraembryonic mesoderm. The epiblast cells that remain on the surface and do not migrate through the streak become the definitive ectoderm.

At the cranial end of the primitive streak, the primitive node organises formation of the notochordal process, which develops into the notochord, a solid rod of mesodermal tissue that defines the axial midline and provides the key inductive signal for the next process, neurulation.

Neurulation is the process by which the neural tube, the precursor of the entire central nervous system, forms from surface ectoderm.

The underlying notochord induces the overlying ectoderm to thicken into the neural plate. The lateral margins of the neural plate then elevate to form neural folds, with a neural groove appearing between them. The neural folds continue to elevate, approach one another in the midline, and fuse, converting the flat neural plate into a hollow neural tube.

Fusion begins in the region of the future cervical spinal cord and proceeds in both cranial and caudal directions simultaneously, with two transient openings, the cranial and caudal neuropores, closing last, around day 24 and day 26 respectively.

Cells at the crest of the neural folds, at the junction between the neural tube and the surface ectoderm, delaminate as the tube closes and become the neural crest. This is a distinct, highly migratory cell population responsible for forming an extensive range of structures throughout the body beyond the nervous system itself.

Folding is the process by which the flat, disc-shaped trilaminar embryo is converted into a three-dimensional, cylindrical body form.

Cephalocaudal folding occurs as the neural tube and somites grow more rapidly than the underlying yolk sac, causing the head and tail regions of the embryo to curl ventrally. Lateral folding occurs similarly along the sides of the embryo, curling the lateral edges of the disc ventrally to meet in the midline.

The combined effect of cephalocaudal and lateral folding is to enclose a portion of the endoderm-lined yolk sac cavity within the body of the embryo, forming the primitive gut tube. It also brings the amnion around to envelop the entire embryo. The connecting stalk, the future umbilical cord, narrows to a defined point of attachment on the ventral surface.

Organogenesis is the formation of individual organs and organ systems from the three germ layers, occurring predominantly across weeks four through eight, and continuing in more limited form somewhat beyond this window for specific systems.

Each organ system follows its own specific developmental programme during this period, but all organogenesis shares common underlying cellular mechanisms: induction between adjacent tissues, directed cell migration, controlled proliferation, progressive differentiation, and, in many structures, programmed cell death to sculpt final form.

By the end of organogenesis, at the close of the embryonic period around week 8, a primordial version of every major organ system exists. Extensive further growth and functional maturation remains to occur throughout the subsequent fetal period.