Wnt and BMP Signaling Govern Lineage Segregation of Melanocytes in the Avian Embryo

Abstract

Recent studies show that specification of some neural crest lineages occurs prior to or at the time of migration from the neural tube. We investigated what signaling events establish the melanocyte lineage, which has been shown to migrate from the trunk neural tube after the neuronal and glial lineages. Using in situ hybridization, we find that, although Wnts are expressed in the dorsal neural tube throughout the time when neural crest cells are migrating, the Wnt inhibitor cfrzb-1 is expressed in the neuronal and glial precursors and not in melanoblasts. This expression pattern suggests that Wnt signaling may be involved in specifying the melanocyte lineage. We further report that Wnt-3a-conditioned medium dramatically increases the number of pigment cells in quail neural crest cultures while decreasing the number of neurons and glial cells, without affecting proliferation. Conversely, BMP-4 is expressed in the dorsal neural tube throughout the time when neural crest cells are migrating, but is decreased coincident with the timing of melanoblast migration. This expression pattern suggests that BMP signaling may be involved in neural and glial cell differentiation or repression of melanogenesis. Purified BMP-4 reduces the number of pigment cells in culture while increasing the number of neurons and glial cells, also without affecting proliferation. Our data suggest that Wnt signaling specifies melanocytes at the expense of the neuronal and glial lineages, and further, that Wnt and BMP signaling have antagonistic functions in the specification of the trunk neural crest.

Microphthalamia-associated transcription factor: a critical regulator of pigment cell development and survival

“…In zebrafish, Wnt has been shown to promote melanocytic differentiation (Dorsky et al, 1998) with MITF as Wnt's downstream effector (Dorsky et al, 2000). These observations have been complemented in higher vertebrates including mouse neural crest cells where Wnt-1 via b-catenin promotes melanocyte differentiation and expansion as well as in chick (Jin et al, 2001). Collectively, these studies have placed the Wnt-signaling pathway as a key cue that stimulates melanocytic diffentiation.…”

Origin of adult‐type pigment cells forming the asymmetric pigment pattern, in Japanese flounder (Paralichthys olivaceus)

“…We consider that a part of this hypothetical asymmetry of organizational environment may be due to the differences in the expression and distribution of secretory proteins involved in the precursor survival and differentiation into mature pigment cells, as Wnt, Bmp, and Noggin, etc. (Dorsky et al, 1998(Dorsky et al, , 2000Jin et al, 2001;Lewis et al, 2004;Raible and Ragland, 2005;Hamre et al, 2007;Hess et al, 2008;Yamaguchi et al, 2008). Thus, we are now examining the expression pattern of the genes encoding the above-mentioned secretory proteins and planning to examine the effect of these secretory proteins on the flounder-specific adult pigment pattern.…”

Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest

“…Neural crest cells are multipotent stem cells that give rise to various cell lineages. A number of signaling molecules, including Wnts, transforming growth factor-␤, and Notch, promote the specification of particular cell fates in neural crest cells (36)(37)(38)(39)(40). Other experiments have shown that osteoblastic cells from embryonic calvarial bones have the potential to differentiate into chondrocytes in vitro (41)(42)(43), suggesting that there are bipotential progenitor cells in these tissues derived from CNC cells, and that there is a degree of plasticity in the cell fate determination of these cells.…”