CLONING AND EARLY DORSAL AXIAL EXPRESSION OF FLIK, A CHICK FOLLISTATIN-RELATED GENE - EVIDENCE FOR INVOLVEMENT IN DORSALIZATION NEURAL INDUCTION

We have cloned and sequenced a chick gene, Flik (follistatin-like) tha t appears to be the homolog of the mammalian TSC36. The ORF encodes a secreted protein of approx 38 kDa, containing a single cysteine-rich d omain that shows a strong relationship with the second of the four fro m which Follistatin is constructed. The remainder of the Flik protein shows no strong family affinities. We describe here the normal express ion pattern of the gene during primitive streak and neurula stages. We also give revised data for early neurectodermal expression of chick f ollistatin (Connolly et al., 1995, Developmental Genetics 17(1), 65-77 ) and follow the new ectopic expression of both genes during the induc tion of a second neural axis, after grafting of Hensen's node into a p eripheral position in a host blastoderm. Both genes mark the organizer (node and/or mesodermal head process) and early neural plate, and cou ld thus be involved in intercellular signaling during mesodermal dorsa lization and neural induction. Flik expression appears earlier than th at of follistatin however, and unlike that of follistatin, it is maint ained strongly in the dorsal midline with intensity smoothly declining into presumptive lateral regions. We show that both genes are upregul ated in host tissue in the neighborhood of node grafts, but whereas fo llistatin is transcribed after 8-10 hr in host epiblast that has forme d new neural plate, Flik is expressed within 4 hr in this region, some times detectable before the first structural changes (columnarization) of neuralization. Thus, although ectodermal Flik expression is later confined within neural plate, and mesodermal expression concentrated i n dorsal axial tissue, its early distribution is consistent with the i dea that the encoded protein may first be involved in generating a gra ded system that positions the boundaries of both neural and dorsal axi al mesodermal territories. The results are discussed in relation to th is hypothesis and to other recent findings regarding control of verteb rate dorsoventral patterning. (C) 1996 Academic Press, Inc.