Normal Development

The eyes begin to develop early in the embryo with the optic grooves forming in the forebrain by week three 15. The optic vesicles begin to form and induce the formation of the lens placode 15. By week four the optic vesicles invaginate into the optic cup and form the retina and optic stalk which is the precursor to the optic nerve 15.

The melanocytes of the eye form from the neural crest cells, while the optic nerve, retina, and posterior iris form from the neuroectoderm 15. The lens forms from the surface ectoderm 15.

Normal Development

Hair develops in four stages: hair bud, hair bulb, hair cone, and the hair and its sebaceous glands 18 . The follicle formation begins during the ninth week of development. Progression occurs in a cephalo-caudal direction 18 .

The hair bud is the first step 18. The hair bud is an epidermal proliferation that enters into the dermis 18.  Second, the hair bulb forms from the hair bud as it becomes longer and more depressed at its distal end 18. The keratinization of the central epithelial cells leads to the third step: formation of the hair cone 18. The epithelial cells create the hair follicle wall, hair epithelial sheath, and the sebaceous glands 18. When the sebaceous gland differentiates and the hair protrudes through the skin the hair follicle formation is complete 18. 

Normal Development

Melanocytes originate as melanoblasts which are cells derived from the neural crest that migrate to the dermal-epidermal junction 21. The melanocytes connect with fibroblasts below them and keratinocytes above them through dendrites and cellular interactions 21. There is 1 melanocyte per 10 basal keratinocytes 21. Melanin is transferred to these keratinocytes from the melanocytes through the dendritic extensions 21. 40 keratinocytes can be melanated by one melanocyte 21.  

Key signaling pathways during development included Wnt/B-catenenin , HOX, FGF, Sonic hedgehog and MC1R-MSH signaling 21. The interplay of these signaling pathways, melanosome Ph, and activity of enzymes such as tyrosinase lead to varying ratios of eumelanin, pheomelanin and the resultant skin color 21.

Disordered Development

One of the hallmark features of Oculocutaneous Albinism is disordered development of the eye 1,16. There are a great proportion of crossing fibers at the chiasm in those with albinism, as well as foveal hypoplasia 16. Hypopigmentation of the retina is consistent in those with albinism as well 17. The result of this disordered development is nystagmus, transillumination of the iris, and poor depth perception 17. 

Disordered Development

During the development of hair, melanocytes originating from neural crest cells migrate to the developing follicles 20. In albinos and normal variants alike, the melanocyte migration to the hair is unimpeded 20. The difference lies in the melanocytes in albinos which do not produce melanin in great quantities due to factors such as no Tyrosinase enzyme activity 20. 

Disordered Development

In disordered pigmentation of skin due to oculocutaneous albinism, the issue is not the number of melanocytes present but their ability to make melanin 21. In albinos they possess the same number of melanocytes as non-albinos 21. The issue stems from an inability to form melanin 21. In normal embryological development, tyrosinase which is a key enzyme in melanin production moves to precursor melanoblasts early on in development 22. This is disrupted in albinos 22.