• When a zygote is undergoing early cleavage division, there must be a way for embryonic cells to differentiate into the cell types that make up the organism
• Strategy 1: Uneven distribution of cytoplasmic determinants in the unfertilized egg
• There are different mRNAs, proteins and other molecules in different regions of the egg cell
• As a result, different factors cause different cells to have different fates
• Additionally, the orientation of the egg gives rise to the orientation of the body axis

• Strategy 2: Once the initial orientation of the organism begins to take form, interactions occur between the embryonic cells
• Cells release chemical signals that cause surrounding cells to “differentiate” in certain ways.
• This process of induction creates the specialized cell types that form different tissues.

• Researchers have discovered the fate of every early cell in the zygote for simple organisms
• Caenorhabditis elegans (type of worm)
• As a result of this research, we have two important conclusions:
• Specific tissue types are developed to early “founder cells”
• As the development of the blastula (developing cellular embro) proceeds, the range of cells that can be created becomes more limited
• This is attributed by the fact that as cells differentiate, they become “fixed” to that cellular fate

• The fact that the developing blastula does not rise uniformly gives rise to asymmetry (later forms the structures of the organism)
• To study this we will first examine how the basic axes of the body are formed
• Organisms that have bilateral symmetry (look the same on the left and right half . . . Humans) must have some basic orientations
• They must have an anterior-posterior axis (top to bottom – head to toe);
• Dorsal-ventral axis (front to back – stomach to back);
• And left and right sides (self explanatory)
• This gives the organism 3D development

• In organisms that do not develop in amniotic fluid, much of the organisms orientation is already determined during oogenesis or fertilization
• Example: Frogs have the their axes determined by positioning of the yolk in the egg
• In organisms with amniotic fluid, body axes are not developed until later in development.
• Example: Chicks have their anterior-posterior axes developed by gravity. Later, pH levels establish dorsal-ventral axes.

• In many vertebrates, the zygote starts out as
totipotent (it can form all types of cells)
• The first cleavage (division) is asymmetrical.
• This causes each of the cells produced to have different cytoplasmic determinants
(chemicals/enzymes that cause different cellular pathways for development)
• In some mammals, the cells in the embryo can remain totipotent until about the 16 cell stage
• In this case, the relative position of the cells determine their differentiation

• Regardless, of how the zygote starts out, cells lose their ability to differentiate as time goes on
• The longer cell development continues, the more a cells “fate” is determined.

• After the general axes of an organism have been determined, cells begin to influence each other through a process called induction
• Release of chemicals that switch on different sets of genes
• This makes the receiving cell differentiate into a specific cell type
• Example: Dorsal cells in frog embryos release a series of growth factors (including Bone morphogenic proteins – BMP)
• These factors cause surrounding cells to differentiate in a specific path (BMP-4 goes down the dorsal side of the frog and induces the formation of the notochord and neural tube (equivalent of spinal chord)

All of these induction pathways lead to a complicated array of signaling that leads to the formation of the organisms form
Another example is the formation of a vertebral limb

• Limbs begin with a bump on the embryonic tissue called limb buds
• Each component of the limb (muscle, skin, bone) develops with a precise location in relation to 3D
• Inductive signaling plays a key role in this
positional information (where the cells are located in relation to each other)
• In general, there are two “organizer” regions that determine limb development
• Apical ectodermal ridge (AER)
• Zone of polarizing activity (ZPA)

• The apical ectodermal ridge is responsible for the outgrowth of the limb
• An analogy is the branch growing out from the trunk of a tree
• This outgrowth is controlled to extend out from the proximal-distal axis (why your arm grows out laterally and not straight out of your chest)

• This is responsible for the anterior-posterior development of the limb
• Includes the orientation of the arm
• Elbows point down not up
• Your hands are oriented correctly so that you do not literally have 2 left thumbs
• Again cells send and receive signals from surrounding cells to orient themselves in relation to other cells