Early Development in Mammals

Cleavage in Mammals

• Fertilization occurs typically in the ampulla of the oviduct close to the ovary

• Meiosis is completed at this time and the first cleavage begins about a day later

• Cleavage in mammals is the slowest in the animal kingdom

– Typically 12 to 24 hours apart

– During cleavage cilia and smooth muscle contractions of the wall of the oviduct push the embryo toward the uterus

Cleavage in Mammals

• First cleavage is meridonal

• In the second cleavage, one of the two blastomeres divides meridionally and the other divides equatorially

– Called rotational cleavage

• The cleavages are also asynchronous - blastomeres do not divide at the same time

– Thus the embryos often have odd numbers of cells rather the 2, 4, 8, 16 and etc

Cleavage Planes in Echinoderms and Mammals

Cleavage in Mouse

Overview of Human Embryo Development

Cleavage in Mammals

• The embryos genome is activated early & produces proteins necessary for cleavage to occur

• In the mouse and goat the switch from maternal to zygotic control occurs at the two cell stage

– Most studies are of murine (mouse) development

Compaction During Cleavage

• Mouse blastomeres through the 8 cell stage form a loose arrangement

• Following the third cleavage - blastomeres suddenly begin to huddle together, maximizing their contact with one another

– They formed a very compact ball of cells

Compaction During Cleavage

Compaction During Cleavage

• This tight arrangement is stabilized by tight junctions that form between the outer layer of cells

– The inner layer is thus sealed off

• Cells within the sphere form gap junctions - small molecules can now pass between the cells

• The next stage is 16 cell morula stage

Morula Stage

• A small group of inner cells is surrounded by a larger group of outer cells

• Most descendents of the external cells become the trophoblast cells

– These cells do not produce embryonic structures

– Forms tissue of the chorion (embryonic portion of the placenta

– Chorion enables the fetus to get oxygen and nourishment form its mother

Morula Stage

• The embryo proper is derived from descendants of the 16-cell stage - supplemented by cells dividing from the trophoblast during transition to the 32 cell stage

– These cells generate the inner cell mass (ICM) - that give rise to the embryo, and its associated yolk sac, allantois, and amnion

Morula to Blastula

• At the 64-cell stage the inner cell mass is about 13 cells and is separate from the trophoblast cells

– Neither contribute cells to the other group

• The distinction between trophoblast and the inner cell mass is the first differentiation event in mammalian development

• This differentiation is necessary for the early mammalian embryo to adhere to the uterus

Morula to Blastula

• Initially morula does not have a cavity - during cavitation - trophoblast cells secrete fluid into the morula to create a blastocoel

• This creates the blastocyst

• This is a hallmark of mammalian cleavage

Escape from the Zona Pellucida

• While the embryo passes through the oviduct the blastocyst enlarges within the zona pellucida

• The cells facing the blastocoel have Na/K pumps that move sodium into the blastocoel - it enlarges (water brought in osmotically)

Escape from the Zona Pellucida

• The zona pellucida initially prevents the blastocyst from adhering to the oviduct wall

– If adherence occurs in the oviduct - tubal or ectopic pregnancy

– This is a potentially life threatening condition because of hemorrhage

• When the embryo reaches the uterus it must hatch from the zona pellucida - then it can adhere to the uterine wall

Escape from the Zona Pellucida

• The mouse blastocyst hatches from the the zona by lysing a small hole in it and then squeezing through the hole

• A trypsin-like protease, strypsin is located on the cell membranes of trophoblast cells - lyses the fibrillar matrix of the zona

Blastocyst Hatching

Implantation

• The trophoblast cells have integrins that bind to the collagen, fibronectin, and laminin of the extracellular matrix of the uterine lining

• Once in contact with the the endometrium, the trophoblast secretes another set of proteases, including collagenase, stromelysin and plasminogen activator

• These digest the extracellular matrix of the uterine tissue

• Now the blastocyst can bury itself within the uterine lining

Implantation of the Blastocyst

Development Within The Mother

• Since mammalian embryos obtains nutrition directly from its mother and not the yoke

– The mother anatomy has to be able to support the embryo - oviduct expands to form the uterus

• Also the embryo itself must be able to absorb nutrients from the mother

• The fetal organ is the chorion - derived primarily from embryonic trophoblast cells, supplemented with mesodermal cells from the inner mass

Development Within The Mother

• The chorion induces uterine cells to form the maternal portion of the placenta

– Called the decidua

• The decidua becomes rich with vessels & will provide oxygen and nutrients to the embryo

Structure of the Placenta

Origins of Early Tissues

• From the inner cell mass

– Hypoblast (primitive endoderm)

– These delaminate from the ICM to line the blastocoel cavity

– Eventually giving rise to the extraembryonic endoderm - forms the yolk sac

– The remainder of ICM - is the epiblast

Origins of Early Tissues

• From the original epiblast

– Embryonic epiblast

– Amnionic ectoderm - forms the amnionic cavity - Fills with amnionic fluid - serves as shock absorber for the embryo

• Also prevents its desiccation

Derivation of Tissues in Primates

Gastrulation in Mammals

• Begins at the posterior end of the embryo

• This is where the node forms (not called Hensen’s node in mammals just “the node”

• Mammalian mesoderm and endoderm migrate through a primitive steak

• These cells just as in the chick lose E-cadherin, detach from their neighbors and migrate through the streak as individual cells

Cell Movements During Gastrulation

Gastrulation

• The cells that form the notochord in the mouse are thought to become integrated into the endoderm of the primitive gut

• These cells are seen as small ciliated cells extending rostrally from the node

• They form the notochord by converging medially and folding off in a dorsal direction from the roof of the gut

Formation of Notochord in the Mouse

Formation of Extraembryonic Membranes

• Initial trophoblast cells give rise to a population of cells - where mitosis occurs without cytokinesis

• The original type of trophoblast cells form a layer called cytotrophoblast

• The multinucleate type of cell forms the syncytiotrophoblast

• The cytotrophoblast cells adhere to the endometrium via several adhesion molecules

– Also contain proteolytic enzymes - can enter the uterine wall - remodel uterine blood vessels - now maternal blood bathes fetal blood vessels

Formation of Extraembryonic Membranes

• Syncytiotrophoblast tissue is thought to further the progression of the embryo into the uterine wall by digesting uterine tissue

• Uterus sends blood vessels into the area - contact the Syncytiotrophoblast

• Mesodermal tissue extends out from the embryo and joins the trophoblast extensions & gives rise to the blood vessels that carry nutrients from the mother to the embryo

• The narrow stalk of mesoderm that links embryo to the trophoblast eventually forms the vessels of the umbilical cord

Formation of Extraembryonic Membranes

• Fully developed extraembryonic organ - consisting of trophoblast tissue & blood vessel-containing mesoderm is called the chorion

• The chorion fuses with the uterine wall to create the placenta

• Fetal and maternal blood never mix

• The mother provides oxygen and nutrients to the fetus and the fetus sends its waste products (CO₂ and urea)

Anterior-Posterior Axis Formation

• Two signaling centers - one in the node and one in the anterior visceral endoderm

• The node seems to be responsible for the creation of all of the body

• The two centers work together to form the forebrain

• The node produces Chordin and Noggin (anterior visceral endoderm do not)

• The anterior visceral endoderm expresses several genes necessary for head formation

Hox Genes

• Hox genes pattern the anterior-posterior axis and help to specify positions along the axis

• Hox gene expression can be seen along the dorsal axis( in the neural tube, neural crest, paraxial mesoderm and surface ectoderm) -from the anterior boundary of the hindbrain through the tail

Hox Genes

• The exact pattern of Hox gene expression is thought to specify the different regions

• The different regions are characterized by different constellations of Hox gene expression

• If Hox genes are knocked out - segment-specific malformations can arise

• Similarly ectopic expression of Hox genes can alter the body axis

Left-Right Axes

• Two levels regulating left-right axes - global level and an organ-specific level

• Similar to that in birds

• The mammalian body is not symmetrical

– Heart begins on the midline but moves to the left side of the chest cavity

– Asymmetrically expressed genes have been discovered