Homeobox genes are a family of genes that encode transcription factors and play a key role in regulating embryonic development and cell differentiation. They were first discovered in 1983 in fruit flies and contain a DNA sequence called the homeodomain that provides instructions for protein production. In humans, there are over 200 homeobox genes located on every chromosome. Homeobox genes establish body patterns and regionalization during development through processes like polarity, positional information, and regulation of genes involved in cell adhesion, migration, proliferation and differentiation. Mutations in certain homeobox genes can lead to developmental disorders and anomalies.

1. Presented By
DARE, Ezekiel & AROGUNDADE, Tolulope
LECTURER: Dr. Ajao M.S.

2. Outline
Introduction
What is geneexpression?
What are homeobox genes?
Discovery
Homeodomain
Human homeotic genes
Body formation
Positional Information
Summary
Clinical Correlations

3. Introduction
Celldifferentiationisthedevelopmentof non-specialisedcellsintocells
withspecialisedfunctions.
Examples: musclecells,livercell,redbloodcells
As organismsgrow and developfrom fertilisedeggs;organs andtissues
developtoproducea characteristicform. Theprocessiscalled
morphogenesis.
Bothprocessesare controlledbygeneexpression

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.

6. Discovery
Homeoboxes were discovered
independently in 1983 by Ernst
Hafen, Michael Levine, and
William McGinnis.
The existence of
homeoboxes was first
discovered in Drosophila.

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.

8. HomeoticGenes
 Master genes of development.

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

10. Other Groupsof HomeoboxGenes

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)

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)

16. Clinicalcorrelations…

17. Synpolydactyly
Synpolydactylyis a joint
presentation
ofsyndactyly (fusion of digits)
and polydactyly (production
ofsupernumerary digits).
This is often a result of a
mutation in the HOX D13
gene.
(Malik etal.,2008)

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.

19. Other AnomaliesAssociated
Axenfeld-Rieger syndrome
branchiootorenal syndrome
coloboma
combined pituitary hormone deficiency
congenital central hypoventilation syndrome
congenital fibrosis of the extraocular muscles
congenital hypothyroidism
craniofacial-deafness-hand syndrome
enlarged parietal foramina
facioscapulohumeral muscular dystrophy
frontonasal dysplasia
Gillespie syndrome
hand-foot-genital syndrome
Langer mesomelic dysplasia
Léri-Weill dyschondrosteosis
microphthalmia
Mowat-Wilson syndrome
nail-patella syndrome
neuroblastoma

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.