Brief Review of Pigment Generation, Part I (BIOL 5104 blog 4)

Melanoblast generation

I would like to write a brief review that covers the processes of pigment generation in chicken. Because of my limit time and effort, this review will be divided into several blogs that posted at most one blog each week.

When we are talking about melanoblast generation, neural crest has to be mentioned. Neural crest is derived from neural tube after gastrula stage. Or more precisely, neural crest cells are specified at the border of the neural plate and the non-neural ectoderm. The first group of cell that differentiated into neural crest cell will migrate ventrolaterally and become neurons and glial. In chicken embryo, one day later (Reedy et al., 1998), the following groups of neural crest cells become melanoblast then migrate dorsolaterally.

So, our first question is what causes the neural tube cells becoming into neural crest cells. At least we know Wnt signaling is in charge of this process, Wnt6 induces neural crest production through the noncanonical signaling pathway and Wnt1 inhibits neural crest induction through canonical signaling pathway. One of the targets of these pathways is FOXD3 (Forkhead box transcriptional repressor, Corina et al., 2007), which is necessary for neural/glial precursors and also can inhibit MITF (Microphthalmia-associated transcription factor, key transcriptional factor for melanoblast formation) expression. So, FOXD3 acts like a switch between neural/glial precursors and melanoblast derived from neural tube, and Wnt6 active FOXD3 while Wnt1 inactive FOXD3. Bone morphogenetic proteins (BMP) also induce FOXD3 during the initial generation of neural crest (Taneyhill and Bronner-Fraser, 2005). Evidence shows that neural crest induction is underway during gastrulation (By expression of the paired box transcription factor PAX7) and well before proper neural plate appearance (when Wnt6 and BMP expressed). But there are other results indicate that the expression of PAX7 is regulated by Wnt6 and BMP (Martı´n L et al., 2006). So, the relationship between PAX7, Wnt6 and BMP in the initiation of neural crest seems unclear.

MITF, a key transcriptional factor for melanoblast formation, is mentioned above. It is activated by PAX3, SOX10 and WNT3A which are exist in neural tube before the formation of neural crest. So MITF should be depressed in other way otherwise the first group of neural crest cell should be melanoblast. That is through the binding of FOXD3 with MITF-M (the melanocyte-specific isoform of MITF) promoter which prevents the binding of PAX3 with this promoter. As FOXD3 is expressed exclusively in the neural/glial precursors, it acts like a key that regulates the lineage switch between neural crest derived glial cells and pigment cells (Aaron et al., 2009). Besides, BMP-4 is expressed in the dorsal neural tube throughout the time when neural/glial precursors are migrating, but is decreased coincident with the timing of melanoblast migration later. This expression pattern suggests that BMP-4 antagonizes melanogenesis (Jin et al., 2001) in conjunction with FOXD3. This lineage switch occurs while the neural crest precursors are still resident in the neural tube.



Reedy, M. V., Faraco, C. D. and Erickson, C. A. The delayed entry of thoracic neural crest cells into the dorsolateral path is a consequence of the late emigration of melanogenic neural crest cells from the neural tube. Dev. Biol. 1998. 200, 234-246.

Corina Schmidt, Imelda M. McGonnell, Steve Allen, Anthony Otto, and Ketan Patel. Wnt6 Controls Amniote Neural Crest Induction Through the Non-canonical Signaling Pathway. Developmental Dynamics. 2007. 236:2502–2511.

Taneyhill, L. A. and Bronner-Fraser, M. Dynamic alterations in gene expression after Wnt-mediated induction of avian neural crest. Mol. Biol. Cell. 2005. 16, 5283-5293.

Martı´n L. Basch, Marianne Bronner-Fraser, Martı´n. Garcı´a-Castro. Specification of the neural crest occurs during gastrulation and requires Pax7. Nature. 2006. Vol 441, 11, 218-222.

Aaron J. Thomas, Carol A. Erickson. FOXD3 regulates the lineage switch between neural crest derived glial cells and pigment cells by repressing MITF through a non-canonical mechanism, Development 136, 1849-1858 (2009).

Jin, E. J., Erickson, C. A., Takada, S. and Burrus, L. W. Wnt and BMP signaling govern lineage segregation of melanocytes in the avian embryo. Dev. Biol. 2001. 233, 22-37.

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