title: Shaping a morphogen gradient for positional precision.
abstract: Morphogen gradients, which provide positional information to cells in a developing tissue, could in principle adopt any nonuniform profile. To our knowledge, how the profile of a morphogen gradient affects positional precision has not been well studied experimentally. Here, we compare the positional precision provided by the Drosophila morphogenetic protein Bicoid (Bcd) in wild-type (wt) embryos with embryos lacking an interacting cofactor. The Bcd gradient in the latter case exhibits decreased positional precision around mid-embryo compared with its wt counterpart. The domain boundary of Hunchback (Hb), a target activated by Bcd, becomes more variable in mutant embryos. By considering embryo-to-embryo, internal, and measurement fluctuations, we dissect mathematically the relevant sources of fluctuations that contribute to the error in positional information. Using this approach, we show that the defect in Hb boundary positioning in mutant embryos is directly reflective of an altered Bcd gradient profile with increasing flatness toward mid-embryo. Furthermore, we find that noise in the Bcd input signal is dominated by internal fluctuations but, due to time and spatial averaging, the spatial precision of the Hb boundary is primarily affected by embryo-to-embryo variations. Our results demonstrate that the positional information provided by the wt Bcd gradient profile is highly precise and necessary for patterning precision.
authors.affiliation: Division of Biomedical Informatics, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Saunders
authors.forename: Ying
authors.initials: Y
authors.lastname: Wen
authors.forename: David
authors.initials: D
authors.lastname: Cheung
authors.forename: Renjie
authors.initials: R
authors.lastname: Jiao
authors.forename: Pieter Rein
authors.initials: PR
authors.lastname: ten Wolde
authors.forename: Martin
authors.initials: M
authors.lastname: Howard
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D019521:Body Patterning; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C056478:bcd protein, Drosophila; C061245:hb protein, Drosophila; C093053:oc protein, Drosophila; C524696:nej protein, Drosophila; D050880:p300-CBP Transcription Factors