Zebrafish spinal cord oligodendrocyte formation requires boc function

From a forward genetic screen for mutations that disrupt oligodendrocyte development in zebrafish, Kearns et al. uncover a new allele of boc, which encodes a co-receptor for the signaling molecule Shh. Shh-dependent spinal cord patterning is normal without boc function, but homozygous mutant embryos fail to maintain ventral progenitors that produce late-born motor neurons and oligodendrocytes. Gene expression analyses reveal that Shh signaling activity shifts dorsally in boc mutant embryos, indicating that Boc helps shape the Shh signaling gradient. Abstract The axis of the vertebrate neural tube is patterned, in part, by a ventral to dorsal gradient of Shh signaling. In the ventral spinal cord, Shh induces concentration-dependent expression of transcription factors, subdividing neural progenitors into distinct domains that subsequently produce distinct neuronal and glial subtypes. In particular, progenitors of the pMN domain express the bHLH transcription factor Olig2 and produce motor neurons followed by oligodendrocytes, the myelinating glial cell type of the central nervous system. In addition to its role in patterning ventral progenitors, Shh signaling must be maintained through development to specify pMN progenitors for oligodendrocyte fate. Using a forward genetic screen in zebrafish for mutations that disrupt the development of oligodendrocytes, we identified a new mutant allele of boc, which encodes a type I transmembrane protein that functions as a coreceptor for Shh. Embryos homozygous for the bocco25 allele, which creates a missense mutation in a Fibronectin type III domain that binds Shh, have normally patterned spinal cords but fail to maintain pMN progenitors, resulting in a deficit of oligodendrocytes. Using a sensitive fluorescent detection method for in situ RNA hybridization, we found that spinal cord cells express boc in a graded fashion that is inverse to the gradient of Shh signaling activity and that boc function is necessary to maintain pMN progenitors by shaping the Shh signaling gradient.