Meeting Abstract

123.4  Tuesday, Jan. 7 14:15  A novel transcriptional regulator, lbh, regulates adaptive craniofacial variation in East African cichlids via neural crest cell migration POWDER, KE*; COUSIN, H; JACOBS-MCDANIELS, NL; ALBERTSON, RC; UMass Amherst; UMass Amherst; Syracuse Univ; UMass Amherst kepowder@bio.umass.edu

Diversification of craniofacial structures to exploit new feeding niches is a cornerstone of adaptive radiations. We have identified, using complementary developmental and evolutionary approaches, a novel modulator of craniofacial development, limb bud and heart homolog (lbh). First, we observed altered lbh expression in a zebrafish model of CHARGE syndrome, which includes defects such as micrognathia and results from abnormal migration of cranial neural crest cells (NCCs), which give rise to the craniofacial skeleton. Second, we determined that a genomic interval containing lbh contributes to variation in mandible length in cichlid fish. Re-sequencing this region in wild-caught populations identified two single nucleotide polymorphisms (SNPs) within lbh that are alternatively fixed (FST=1.0) in two cichlid species with differing jaw morphologies, including one micrognathic species. One of these SNPs is intronic and the other encodes a non-synonymous change within a region necessary for the transcriptional activity of lbh. To expand on these putative roles of lbh in craniofacial disease and evolution, we evaluated the function of lbh in NCC and facial development. We observed lbh expression in NCCs, and found that depletion of Lbh results in cell-autonomous inhibition of NCC migration and discrete facial defects including a severe reduction of the lower jaw precursor. Notably, Lbh variants isolated from cichlids with alternate jaw morphologies differentially regulate NCC migration. These data strongly implicate lbh as a mediator of both clinical and evolutionary micrognathism, and suggest a cellular mechanism of adaptive craniofacial evolution in cichlids.