Embryology- polarity

  • How is a multicellular organism made?
  • Patterns?

Gradients to Axes Morphogenesis to Differentiation.

Homeobox Genes Growth Factors,- cell adhestion molecules & extracellular Matrix

Polarity

 

"The more things change, the more they stay the same."

 

Despite profound differences between fly and vertebrate embryos and a large evolutionary separation, mechanisms for regulating pattern formation appear homologous (similar).

Early development

Fly- syncytium

Vertebrate- cellular aggregate (blastula or blastocyst)

Genetic analysis of fly mutations led to the discovery of genes that are important in early development.

Maternal regulatory systems establish the initial asymmetry by positioning (maternal) transcription factors asymmetrically in the developing embryo.

Transcription factors turn genes on or off

Asymmetry amplified by a cascade of zygotic transcription factors which polarized the embryo by the time of cellularization, leads to a segmented body pattern.

Diversity within the segments driven by homeotic genes selector genes (which encode transcription factors). These genes were identified by mutations which turned one segment into another.

Bithorax

 

Antennapedia

Homeotic genes represent the switch from global regulation by maternal and early zygotic products to differential specification of tissue types -> -> -> body structures.

Homeotic genes

  • encode transcription factors
  • are organized in clusters and transcribed in the same direction
  • (drosophila, 2 clusters Chromosome 3)
  • (mouse & human 4 clusters HOX genes on different chromosomes)
  • are positioned and expressed in sequence
  • this order corresponds to head -> tail
  • act on other selector genes and themselves (autoregulation)
  • expression pattern analysed by in situ hybridization
  • (identifies where the mRNA is found, bands of expression)
  • mainly expressed in CNS and somitic mesoderm (mouse 6.5d head-tail axis)
  • generates defined segregates of cells into compartments

Growth Factors

 Very early axis decisions must be different

The early syncytium of fly development allows a gradient of morphogen(s), a maternal transcription factor (bicoid, nanos, gurken) to encode positional information in the early embryo. This gradient is established by transporting and anchoring maternal bicoid mRNA to one end of the embryo.

This would not work for cellular (blastula) development.

In blastula axis formation, rather than an intrinsic morphogen gradient an extrinsic morphogen growth factor gradient appears to act.

 

 

Frogs (Xenopus)

  • Vertebrate and blastula development
  • Inductive interactions

One group of cells (1) signals to a second group of cells (2) in such a way as to determine the developmental fate of the second.

Requires a capacity to signal (1) and an ability to respond (2).

These signals have been identified as growth factors (released from 1) that act through specific receptors on the cell surface (2). activin, Vg1, FGF