4. What is geneexpression?
Gene expression is the
activation of a gene that results
in a polypeptide or protein.
Transcription factors
5. What are HomeoboxGenes?
Homeoboxgenesare a large family of similar genes that
direct the formation of many body structures during early
embryonic development.
The gene is a unit of information that encodes a genetic
characteristic.
7. Homeodomain
Homeobox genes contain a
particular DNA sequence that
provides instructions for making a
string of 60 protein building blocks
(amino acids) known asthe
homeodomain.
9. Human HomeoboxGenes
In humans, the homeobox gene family
contains anestimated 235 functional
genes and 65 pseudogenes.
Homeobox genes are present on every
human chromosome, and they often
appear in clusters.
Examples include: HOX, PAX, MSX, DLX
11. Four general phasesfor body
formation
1. Organizebodyalong
major axes
2. Organizeinto smaller
regions (organs, legs)
3. Cells organize to
produce body parts
4. Cells themselves
change morphologies
and become
differentiated
12. ModusOperandi
Polarity
•Even before fertilization an egg has a gradientof proteins that help to
establish its polarity (which end becomesthe head or anterior and which
is the tail, posterior)
•After fertilization “Maternal Effect” genes reinforce this polarity and also
establish the dorsal (back)and ventral (belly) orientation
•Polarity is the formation of the axis by which the embryo differentiates
13. Positional informationduring development
• Eachcell receives positional
information that tells it where to go
and what to become.
• Cells may respond by
1. Cell division,
2. cell migration,
3. cell differentiation or
4. cell death (apoptosis)
14.
15. Summary
Three-dimensional patterning and body plan formation during
embryogenesis arelargely attributable toaction of homeobox genes,dueto
their capacity to spatiotemporally regulate the basic processes of
differentiation, proliferation, and migration (Manley and Levine, 1985; Han
etal., 1989).
Homeobox genes can regulate genes responsible for cell adhesion,
migration, proliferation, growth arrest, and the expression of cytokines
neededfor extracellular matrix interactions (Graba etal.,1997; Svingen and
Tonissen, 2006; Hueber etal., 2007)
18. Aniridia
Aniridia is an eye disordercharacterized by a
complete or partial absence of the colored part
of the eye (the iris).
Aniridia is causedbymutations in
the PAX6gene.The PAX6geneprovides
instructions for making a protein that is
involved in the early development of the eyes,
brain and spinal cord (central nervous system),
and the pancreas.
20. References
• McGinnis W, Levine M, Hafen E, Kuroiwa A,GehringW (1984)."Aconserved DNAsequence inhomoeotic genes
of the Drosophila Antennapedia and bithorax complexes". Nature308(5958):428–33.
• Scott M, WeinerA (1984)."Structural relationships among genes that control development: sequence homology
between the Antennapedia, Ultrabithorax, and fushi tarazu loci of Drosophila". Proceedings of the National
Academy of Sciencesof the UnitedStates of America 81 (13): 4115–9
• Graba, Y.,Aragnol, D., and Pradel, J. (1997).Drosophila Hox complex downstream targets and the function of
homeotic genes. Bioessays 19,379–388
• Han, K., Levine, M. S., and Manley,J. L. (1989). Synergisticactivation and repression of transcription by Drosophila
homeobox proteins. Cell 56,573–583.
• Manley,J. L., and Levine, M. S. (1985).The homeo box and mammalian development. Cell 43,1–2. doi:
10.1016/0092-8674(85)90002-9
• Hueber, S. D., Bezdan, D., Henz, S. R., Blank, M., Wu, H., and Lohmann,I. (2007).Comparative analysis of Hox
downstream genes inDrosophila. Development 134,381–392.
• Svingen, T., and Tonissen, K. F. (2006).Hox transcription factors and theirelusive mammalian gene targets.
Heredity (Edinb.) 97, 88–96.
Editor's Notes
The expression of some genes results in the production of a protein that can turn on or switch off other genes.
Every organism has a unique body pattern because of the influence of HOMEOBOX genes.
These specify how different areas of the body develop their individual structures, eg. Arms, legs etc
Homeobox genes were discovered when geneticists studying fruit flies found mutants with legs growing where their antennae should be and 2 sets of wings instead of 1.
Homeotic genes are regulatory genes that determine where certain anatomical structures, such as appendages, will develop in an organism during morphogenesis.
These seem to be the master genes of development
For example, mutations in the HOX group of homeobox genes typically cause limb malformations. Changes in PAX homeobox genes often result in eye disorders, and changes in MSX homeobox genes cause abnormal head, face, and tooth development. Additionally, increased or decreased activity of certain homeobox genes has been associated with several forms of cancer later in life.
Once the orientation is in place other genes are switched on
Segmentation occurs driven by Gap genes, Pair rule Genes and Segmentation genes
Finally the Homeotic Selector genes are switched on
These control the final specialised development of each segment
See Page 114 Text book
Each cell in the body must become the appropriate cell type based on its relative position.