Human Development Chap 7

Zygote --> Multicellular organism

• Axis formation (begins as early as oocyte formation)  
• Anterio-Posterior (Head – Anus) 
• Dorso-Ventral (Back – Belly) 
• Left-Right

• This process involves two critical stages: 
• Cleavage – rapid cell division  Gastrulation – displacement of cells to new neighborhoods

Biphasic cell cycle of early Blastomeres: M (Mitosis) and S (DNA synthesis) phases– Cyclin synthesis allows progression to M phase-Differentiating cells are taken out of cell cycle (G0)-Cyclins and their respective kinases are stage specific regulation of cell cycle-After numerous synchronous rounds of mitosis, cells begin to go their own way.

• Karyokinesis is usually followed by cytokinesis

Microtubules - spindle fibers

Actin microfilaments - contractile ring (cleave furrow)

• Cleavage – series of mitotic divisions divide egg cytoplasm into numerous smaller nucleated cells, “blastomeres”

• During early divisions there is no increase in cytoplasm between cell divisions
• Egg cytoplasm --> ½ --> ¼ -->1/8 -->

• Frog egg --> 37,000 cells in 43 hrs
• Drosophila egg --> 50,000 cells in 12 hrs

• Polarity of Eggs - Unequal distribution of cytoplasmic contents.
• Animal pole – less yolk --> faster cell divisions Vegetal pole - Yolk rich pole --> slower cell divisions.

• Patterns of cleavage are determined by:
• 1.Amount of yolk protein determines where cleave can occur and relative size of blastomeres.
• 2. Factors in egg cytoplasm influence angle of mitotic spindle and timing of its formation

• •Holoblastic – complete – (cleave furrow extends through out the embryo)
•        Ex: Isolecithal and Mesolecithal eggs
• •Meroblastic – Incomplete
•        Ex: Telolecithal and Centrolecithal eggs

Isolecithal – Echinoderms



Mesolecithal–Amphibians



Telolecithal – Birds



Centrolecithal - Insects

• Rearrangement of cells in Blastula- Highly coordinated cell movements --> new position, new neighborhoods establishment of multilayered body plan
• 3 germ layers
• –Ectoderm  - Outside 
• -Mesoderm  - Middle 
• -Endoderm  - Inside

• - cells forming endodermal and mesodermal organs are brought in
• - cells forming skin and outer layers are spread over

Invagination: Infolding of cell sheet into embryo – eg. S. U.endoderm

Involution: Inturning of cell sheet over basal surface over an outer layer – eg. A. mesoderm

Ingression: Migration of individual cells into the embryo – eg. S.U. mesoderm

Delamination: Splitting or migration of one sheet into two sheets – eg. Bird or mammalian hypoblast formation

Epiboly: expansion of one cell sheet over other cells – eg. Enctoderm formation in S.U., A.

• Anteroposterior axis: Head to tail (or anus)

• Dorsovental axis:  Back to belly – in vertebrates the neural tube is dorsal and insects the neural cord is ventral
• -Midsagittal

• Right-left axis: Two lateral sides of the body – position of liver and heart on the left side of the body
• -Horizontal plane

• 1st cleavage -  Meridional - 2 cells
• 2nd cleavage - Meridional (perpendicular to first   one)   – 4 cells
• 3rd cleavage – Equatorial – 8 cells

• 4th cleavage:
• – 4 cells in animal pole divide meridionally --> 8 cells of equal volume called mesomeres
• - 4 cells in the Vegetal pole divide unequally to give rise 4 large macromeres and 4 small micromeres
• Next cleavage – 4 tiers of cells;
• - mesomeres --> an1, an2; macromeres --> veg1, veg2;Micromeres divide slowly --> form a cluster of cells

• Blastula - 128 cell stage – hollow sphere of cells surrounding central cavity called balstocoel.
• Tight junctions unite loosely connected blastomeres.

The decrease in cytoplasm triggers activation of certain genes --> ending synchronous cell divisions

-Non-dividing cells develop cilia on their outer surface.

-Ciliated blastula begins to rotate within the fertilization envelope

-Cells at vegetal pole begin to thicken --> vegetal plate



Cells in Animal half secrete proteolytic enzymes --> digest the fertilization envelope --> hatching of free-swimming blastula

• Animal
• half --> ectoderm --> skin and neurons

Veg1 --> either ectodermal or endodermal organs

• Veg2 --> endoderm, coelom and secondary   mesenchyme (pigments cells, immunocytes
•   and muscle cells)

Micromeres --> influence specification of veg2 layer --> which in turn specify veg1 layer to produce endoderm 

• Micromeres
• produce signaling molecules – the b-catenin (a transcription factor)

• Specification
• involves a cascade of events:

• b-catenin --> post-translational modification of factors in veg2 layer --> modifies a transcription factor in veg1
• layer --> specification of cells

Eric Davidson’s, Caltech, Pasadena, CA pioneered network approach to development

The networks would receive its first inputs from transcription factors located in cytoplasm.

Skeletogenic mesenchyme cells of sea urchin are specified autonomously to ingress into the balstocoes --> become skeleton of plutus larva

•During oogenesis Desheveled becomes located in the vegetal cortex of the egg -->prevents degradation of b-catenin

•b-catenin enters and accumulates in the nuclei of those cells fated to become endoderm and mesoderm

•Treating sea urchin embryos with Lithium chloride causes accumulation of b-catenin in every cell causing presumptive ectoderm into endoderm --> failure of gastrulation

A – Normal development

B. Isolated animal hemisphere --> becomes only ciliated ball of ectodermal cells

C. When isolated animal hemisphere combined with isolated micromeres --> recognizable larva

Conditional specification: Cells are committed to form specific tissue type depending on the location

These cells are pluripotent --> can give to other cells if placed in different parts of embryo

Autonomous Specification: Cells are committed irrespective of location

Eg: Fate of skeletogenic micromeres are determined autonomously --> wherever they are transplanted, they will form only skeletal spicules

• Transplanted
• micromeres: 

-Invaginate at the new site --> to produce new primary mesencyme cells

-Induce new animal pole cells to form vegetal plate endodermal cells

-Differentiate into skeletal rods

• Animal–Vegetal
• axis determines the future Anterior-Posterior axis

  Vegetal axis sequesters maternal   components (factors) necessary for   posterior development

• Dorsal-Ventral
• axis and right-left axes are specified after fertilization – becomes visible in
• 8-cell stage

Blastula develops into Pluteus larva through Gastrulation involving movement of cells

The Vegetal side of Blastula thickens and flatten – Vegetal plate

Ingression of Primary Mesenchyme:

• Micromeres at the Vegetal plate develop filopodia --> dissociate from other cells à
• ingress into blastocoel --> form primary mesenchyme --> gives rise to larval skeleton (skeletogenic mesenchyme)

• Guidance for Ingression:
• once in the blastocoel, the primary mesenchyme cells migrate along extracellular matrix

Migration is further assisted by fibronectin and sulfate glycoproteins

Ultimately these cells stop at a particular position

• Archenteron – primitive gut is formed by Invagination of marcomeres
• at Vegetal plate. Occurs in 3 stages

First Stage: Hyaline layer at the Vegetal plate is composed of two layers, outer lamina with hyaline protein and inner lamina with fibropellin protein

Vegetal plate cells secrete Chondroitin sulfate proteoglycan into inner lamina --> absorbs water --> swells only inner lamina --> buckling of hyaline layer




Second stage of Invagination:

Convergent extension – secondary mesenchymal cells migrate over one another and by flattening themselves

Cell division also contributes to the extension

• Third stage:
• Cells at the tip of growing archenteron extend filopodia --> contact with inner wall of blastocoel --> these contacts shorten --> pulling up of archenteron to the target site

Target site is specific, which ultimately forms the mouth

Blastopore becomes Anus