Annotated Bibliography
Aruga, J.(2004). “The role of Zic genes in neural development”. Mol cell Neurosci.,
26(2):205-21. [http://www.ncbi.nlm.nih.gov/pubmed/15207846 PMID:1
5207846].
In this study, Aruga reviews studies done on the Zic family. Zic family is
essential in neural development including neurulation and cerebral
patterning. Zic2 is responsible for determining ipsilateral projecting axons
and it present in RGC layer at E16.5 when these projections occur. It is
necessary to repulse the ipsilateral axons away from the midline.
Baxter, L.L., Hou, L., Loftus, S.K. and Pavan, W.K. (2004). “Spotlight on spotted mice:
a review of white spotting mouse mutants and associated human pigmen
tation disorders”. Pigment Cell Res., 17(3):215-24. [http:/
/www.ncbi.nlm.nih.gov/pubmed/15140066 PMID:15140066].
Clegg, D.O., Buchholz, D., Hikita, S., Rowland, T., Hu, Qirui and Johnson, L.V. (2008).
“Retinal Pigment Epithelial Cells: Development In Vivo and Derivation from
Human Embryonic Stem Cells In Vitro for Treatment of Age-related Macular
Degeneration”. Advances in Biomedical Research, 1:1-24. [DOI: 10.1007/9781-4020-8502-4_1].
Zic2 is a transcription factor regulated by homeobox transcription factors
necessary for eye formation in vertebrates such as Rax and Six3. Mitf is one
of the master regulator of retinal pigment epithelial cells which activate
melanin pigment synthesis genes such as tyrosinase.
Cronin, C.A., Ryan, A.B., Talley, E.M., and Scrable, H. (2003). “Tyrosinase Expression
during Neurblast Divisions Affects Later Pathfinding by Retinal Ganglion
Cells.” J. Neurosci., 23(37):11692-11697.
[http://www.ncbi.nlm.nih.gov/pubmed/14684871 PMID:14684871].
In this study, Cronin et al. examines the effect of tyrosinase expression on
neuroblast division. Visual defects in oculacutaneous albinism results from
mutation in tyrosinase. Expression of tyrosinase must occur at E10.5-13
during period of neuroblast division to give rise to proper ratio of ipsilateral
RGCs. Timing of tyrosinase expression is required for correct neuroblast
division as it affects the ability of RGC to express of recognize unidentified
guidance cues. Albinos display disruptions in early neurogenesis and cell
cycle kinetics.
Engle, E.C. (2010). “Human Genetic Disorders of Axon Guidance”. Cold Spring Harb
Perspect Biol., 3(1). [doi: 10.1101/cshperspect.a001784].
In this study, Engle describes the phenotypes of ocular albinism and
oculocutaneous albinism. Characteristics include increased contralateral
projection axons, decreased ipsilateral projection axons and foveal
hypoplasia. The author hypothesized that melanin might provide positional
information for axon migration.
Guibal, C. and Baker, G.E. (2009). “Abnormal Axons in Albino Optic Tract”. Invest
Opthalamo Vis Sci., 50(12):5516-21.
[http://www.ncbi.nlm.nih.gov/pubmed/19628745 PMID:1962874].
In this study, Guibal and Baker found that albinos posses abnormal axons.
Albinos display abnormal ratio of ipsilateral to contralateral RGCs as a
consequence of abnormal timing of their cell outgrowth. Albinism occurs
from disruption of tyrosinase expression. Phenotype includes reduced
pigmentation, disorganized retinal epithelium, underdeveloped fovea and
misrouted RGCs. Albino ferrets display abnormal ratio between axon
diameter and myelin thickness.
Herrera, E., Brown, L., Aruga, J. Rachel, R.A., Dolen, G., Mikoshiba, K., Brown, S. and
Mason, C.A. (2003). “Zic2 patterns binocular vision by specifying the
uncrosssed retinal projection”. Cell, 114(5):545-57. [
http://www.ncbi.nlm.nih.gov/pubmed/13678579 PMID:13678579].
In this study, Herrera et al. demonstrate that Zic2 is expressed in retinal
ganglionic that grow ipsilaterally from ventrotemporal retina toward the
optic chiasm. Loss-of-function and gain-of-function experiments show that
Zic2 is necessary and sufficient to make cells grow away from the optic
chiasm midline.
Petros, T.J., Rebsam, A. and Mason, C.A. (2008). “Retinal axon growth at the optic
chiasm: to cross or not to cross.” Annu. Rev. Neurosci., 31:295-315. [http:/
/www.ncbi.nlm.nih.gov/pubmed/18558857 PMID:18558857].
In this study, Petros et al. review studies on albinos and the abnormal
ipsilateral ratio. Higher vertebrates species require visual field of each retina
to connect to both sides of the brain. In human, 40% of RGCs are ipsilateral.
Optic chiasm is established at three different stages. Zic2 is downregulated in
albinos. It is unclear how melanin impacts this pathway.
Rachel, R.A., Dolen, G., Hayes, N.L., Lu, A., Erskine, L., Nowakowski, R.S. and Mason,
C.A. (2002). “Spatiotemporal features of early neuronogenesis differ in wildtype and albino mouse retina”. J. Neurosci., 22(11):4249-63.
[http://www.ncbi.nlm.nih.gov/pubmed/12040030 PMID:12040030].
In this study, Rachel et al. found that ocular and oculocutaneous albinism had
increased ganglionic cells, abnormal cellular organization and reduced
retinal ganglionic cell differentiation. Increased proliferation is also reported.
Shibahara, S., Takeda, K., Yasumoto, K., Udono, T., Watanabe, K., Saito, H. and
Takahashi, K. (2001). “Micropththalmia-Associated Transcription Factor
(MITF): Multiplicity in Structure, Function, and Regulation.” Journal of
Investigative Dermatology Symposium Proceedings, 6: 99-104.
[doi:10.1046/j.0022-202x.2001.00010.x].
Mitf is a basic-helix-loop-helix-leucine-zipper transcription. It activates genes
crucial in melanin synthesis. Alternative splicing of Mitf gene can produce at
least 5 isoforms with different N-termini. Melanocyte-specific Mitf-M is most
common isoform but is not found in RPE. Mitf-A and Mitf-H are expressed in
RPE.
Vetrini, F., Auricchio, A., Du, J., Angeletti, B., Fisher, D.E., Ballabio, A. and Marigo, V.
(2004). “The Micropthlamia Transcription Factor (Mitf) Controls Expression
of Ocular Albinism Type 1 Gene: Link between Melanin Synthesis and
Melanosome Biogenesis.” Mol. Cell. Biol., 24(15):6550.
[http://www.ncbi.nlm.nih.gov/pubmed/15254223 PMID:15254223].
Melanin is produced in melanosome. Albinism results from mutations in
genes involved in melanin synthesis or melanosome biogenesis. Mitf is
important in development and differentiation of melanocytes in skin and eye.
Mutation results in albinism-deafness syndrome (Tietz). It activates TYR and
TRP with its M-box.