April 28, 2024

The Primitive Streak and Building a Human Body Through Gastrulation

After fertilization, a human embryo implants into the uterus (day 6-12) and gastrulation begins soon later on, with the primitive streak emerging at about day 14. Gastrulation assigns cell fates and spatial collaborates to epiblast cells, setting the foundation of the human body. Credit: Dr. Guojun Sheng; Credit for the “Fetus in the womb” sketch by Leonardo Da Vinci: Royal Collection Trust/ © Her Majesty Queen Elizabeth II 2021
The very first provides cells spatial identities along the anteroposterior (head-to-tail) and dorsoventral (back-to-front) axes. The 2nd organizes cells into groups (i.e., germ layers).
In many animals, consisting of humans, there are 3 bacterium layers: the ectoderm (source of the skin, nerve system, eyes, etc), the mesoderm (source of the muscles, bones, vessels, and so on) and the endoderm (source of the intestines, lungs, liver, pancreas, etc).
When a little number of pluripotent and dividing cells start the differentiation process in these 2 coordinate systems, one of the most important durations of advancement occurs. In human development, this takes place at around two weeks after fertilization through a process called gastrulation and is associated with an embryonic structure called the primitive streak– a structure in early development that starts bilateral symmetry and germ layer formation.

Like a boulder rolling down the side of a mountain, a gastrulating cell start a journal of no return, culminating in its terminal distinction into among a number of hundred cell family trees that comprise human tissues and organs. With technical advancements in revitalizing differentiated cells back into a naïve state pioneered by researchers like John Gurdon and Shinya Yamanaka (2012 Nobel Prize winners), scientists worldwide are now able to grow pluripotent, pre-gastrulation human (and other mammalian) cells in the laboratory, and through step-by-step addition of biochemical hints, guide these cells to differentiate into any among numerous cell family trees. However, cultivating these cells into functioning tissues or organs has seldom achieved success.
One reason for this failure is that organogenesis (the procedure of organ formation) in vivo begins instantly after gastrulation when cells of different bacterium layer origins and spatial coordinate identities work together in making fundamental organs. Through subsequent reciprocal interactions, these cells undergo organ- and species-specific expansion, three-dimensional company, and terminal differentiation before reaching functional maturity. Reproducing (recapitulating) such organ aspects in vitro therefore has ended up being the holy grail in stem cell biology and regenerative medicine research.
Accomplishing this would require recapitulation of gastrulation and its associated primitive streak. Nevertheless, neither gastrulation nor the primitive streak has been rigorously analyzed in human development, and comparative views of animal gastrulation and the primitive streak in the literature are typically incorrectly depicted.
Now, through an organized evaluation of previous research study, Prof. Sheng and associates offer evidence that the primitive streak is not a conserved function in amniote advancement, and that avian and mammalian primitive streaks developed separately, utilizing various supra-cellular systems that result in their morphological emergence.
The researchers stress that, in addition to moderating the introduction of germ layers from the epiblast (pluripotent cells), the primary role of gastrulation is to confer newly formed cells in each bacterium layer a coordinate system to arrange primary cell fates and the primordia of organs and tissues that are relative to each other spatially.
Their analyses of various biomechanical specifications in between multiple in vivo and in vitro models predict that a rudimentary mammalian body plan can form in the absence of a primitive streak. They also recommend that the “14-day rule” (where a human embryo can not be cultured 14 days past fertilization or after the appearance of the primitive streak), which is currently used in numerous nations as the essential ethical oversight in human embryological research, need to be re-assessed and an alternative landmark be picked through a consensual conversation between various stakeholders to ensure ethical and clinical rigor.
Recommendation: “The primitive streak and cellular concepts of constructing an amniote body through gastrulation” by Guojun Sheng, Alfonso Martinez Arias and Ann Sutherland, 3 December 2021, Science.DOI: 10.1126/ science.abg1727.

Gastrulation assigns cell fates and spatial coordinates to epiblast cells, laying down the structure of the human body. With technical advancements in rejuvenating separated cells back into a naïve state originated by scientists like John Gurdon and Shinya Yamanaka (2012 Nobel Prize winners), scientists worldwide are now able to grow pluripotent, pre-gastrulation human (and other mammalian) cells in the laboratory, and through stepwise addition of biochemical cues, guide these cells to distinguish into any one of hundreds of cell lineages. One factor for this failure is that organogenesis (the process of organ development) in vivo starts instantly after gastrulation when cells of different germ layer origins and spatial coordinate identities cooperate in making primary organs. Through subsequent mutual interactions, these cells undergo organ- and species-specific proliferation, three-dimensional organization, and terminal distinction before reaching functional maturity.