Homeobox genes are a large family of genes that regulate embryonic development. They were first discovered in fruit flies and contain a DNA sequence called the homeodomain that encodes a protein regulating transcription of other genes. In humans, homeobox genes are organized into four clusters (A-D) on different chromosomes and regulate body patterning along the head-to-tail axis. Mutations in homeobox genes can lead to developmental disorders like aniridia, synpolydactyly, and Axenfeld-Rieger syndrome. There is potential to use homeobox genes like PDX-1 in gene therapy to generate new tissues like pancreatic beta cells in the liver to treat diseases like diabetes.
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Homeobox genes
1. HOMEOBOX GENE
BY
ADESEJI WASIU ADEBAYO
08/46KA006
Department of Anatomy,
University of Ilorin
ANA 811:MOLECULAR EMBRYOLOGY AND GENETIC
ENGINEERING
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3. What are HomeoboxGenes?
•Homeoboxgenesare a large family of similar genes thatdirect and
regulate the formation of many body structures during early embryonic
development.
•Homeobox is a DNA sequence, around 180 base pairs long, involved in
the regulation of patterns of anatomicaldevelopment (morphogenesis) in
animals,fungi and plants.
•The gene is a unit of information that encodes a genetic characteristic.
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4. Discovery
•Homeoboxes were discovered independently in
1983 by Ernst Hafen, Michael Levine, and William
McGinnis in Basel (McGinnis et al., 1984) and
Matthew P. Scott and Amy Weiner in Bloomington
(Scott and Weiner, 1984).
•The existence of homeoboxes
was first discovered in fruit fly
(Drosophila melanogaster). 4
5. Homeodomain
•Homeobox genes contain a 180 base pairs DNA sequence that
provides instructions for making a string of 60 amino acids protein
building blocks known as the homeodomain.
•Homeodomain act astranscription factors,
o Bind to DNA and controls transcription of other genes in the
cell
o Initiate patterns of gene expression
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7. HUMAN HOX GENE
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Human hox genes are collected into homeotic clusters.
o There are 4 homeotic clusters, labelled A,B,C and D,
o Each cluster is situated on a different chromosome.
o Each homeotic cluster consists of 13 homeotic genes numbered
sequentially from 1 to 13.
8. HUMAN HOX GENE
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The four numerically corresponding genes for the four different clusters form a
paralogous group.
o The hox genes are responsible for patterning along the antero-posterior axis.
o The genes are expressed sequentially beginning with the paralogous group 1,
which is expressed first
o The sequential genes specify different segments in cranio-caudal sequence
extending from paralogous group 1, which specifies the most cranial structures,
to paralogous group 13, which specifies the most caudal structures.
o Thus the first genes to be expressed specify the most cranial structures while
the last to be expressed specify the most caudal structures. This is responsible
for the cranio-caudal sequence of development, where the more cranial
segments develop slightly before the more caudal structures. Consequently the
upper limb develops ahead of the lower limb.
10. DISTAL-LESS GENE (Dlx)
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• Dlx genes are involved in the development of the nervous system and of
limbs.
• Dlx 1 and Dlx 2 are expressed by migrating cortical interneurons during
neurogenesis.
• Other members of the distal-less homeobox group are DLX1, DLX2,
DLX3, DLX4, DLX5, and DLX6.
12. Classes of Human Homeoboxes
1. ANTP class homeoboxes
6. SINE class homeoboxes
HOXL subclass homeoboxes
7. TALE class homeboxes and
pseudogenes
NKL subclass homeoboxes and
pseudogenes
8. CUT class homeoboxes and
pseudogenes
2. PRD class homeoboxes and
pseudogenes
9. PROS class homeoboxes
3. LIM class homeoboxes
10. ZF class homeoboxes and
pseudogenes
4. POU class homeoboxes and
pseudogenes
11. CERS class homeoboxes
5. HNF class homeoboxes
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13. FUNCTIONS OF HOMEOBOX
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• Three-dimensional patterning and body plan formation during embryogenesis are largely
attributable to action of homeobox genes, due to their capacity to spatiotemporally
regulate the basic processes of differentiation, proliferation, and migration (Manley and
Levine, 1985; Han et al., 1989).
• Homeobox genes can regulate genes responsible for cell adhesion, migration,
proliferation, growth arrest, and the expression of cytokines needed for extracellular
matrix interactions (Graba et al., 1997; Svingen and Tonissen, 2006; Hueber et al., 2007)
19. HOMEOBOX GENE AND GENETIC
ENGINEERING
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Can we create new organs from our own tissues?
In a study to review potential future methods of curing metabolic disorders such as diabetes, and analyze the
capacity to genetically manipulate the developmental fate of a tissue in vivo using "master regulator" genes.
• the homeobox gene Pancreatic and Duodenal Homeobox gene-1 were systemically delivered to liver of
mice, by recombinant adenovirus technology, and analyzed whether it induces a developmental shift toward a
beta cell phenotype
• PDX-1 is sufficient to activate the endogenous, otherwise silent, mouse insulin 1 and 2 and pro-insulin
convertase gene expression in liver.
• PDX-1 expression in liver resulted in a 25-fold increase in hepatic immunoreactive insulin content and a
threefold increase in plasma immunoreactive insulin levels, as compared to control adenovirus-treated mice.
(Ferber, 2000).
20. CONCLUSION
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• Homebox genes are very important factor in normal morphogenesis in animals including human.
• Mutations of these groups of gene lead to abnormal formation of structures.
• Homebox genes might be the gateway in the field of genetic engineering to create new organs from our
own tissues
21. REFERENCES
• McGinnis W, Levine M, Hafen E, Kuroiwa A, Gehring W (1984). "A conserved DNA sequence in homoeotic genes
of the Drosophila Antennapedia and bithorax complexes". Nature 308 (5958): 428–33.
• Scott M, Weiner A (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 Sciences of the United States 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). Synergistic activation and repression of transcription by Drosophila
homeobox proteins. Cell 56, 573–583.
• Ferber S. (2000). Can we create new organs from our own tissues? Isr Med Assoc J. 2 Suppl:32-6.
• 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 in Drosophila. Development 134, 381–392.
• Svingen, T., and Tonissen, K. F. (2006). Hox transcription factors and their elusive mammalian gene targets. Heredity
(Edinb.) 97, 88–96. 21
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