title: Maternal origins of developmental reproducibility.
abstract: Cell fate decisions during multicellular development are precisely coordinated, leading to highly reproducible macroscopic structural outcomes [1-3]. The origins of this reproducibility are found at the molecular level during the earliest stages of development when patterns of morphogen molecules emerge reproducibly [4, 5]. However, although the initial conditions for these early stages are determined by the female during oogenesis, it is unknown whether reproducibility is perpetuated from oogenesis or reacquired by the zygote. To address this issue in the early Drosophila embryo, we sought to count individual maternally deposited bicoid mRNA molecules and compare variability between embryos with previously observed fluctuations in the Bicoid protein gradient [6, 7]. Here, we develop independent methods to quantify total amounts of mRNA in individual embryos and show that mRNA counts are highly reproducible between embryos to within ~9%, matching the reproducibility of the protein gradient. Reproducibility emerges from perfectly linear feedforward processes: changing the genetic dosage in the female leads to proportional changes in both mRNA and protein numbers in the embryo. Our results indicate that the reproducibility of the morphological structures of embryos originates during oogenesis, which is when the expression of maternally provided patterning factors is precisely controlled.
authors.affiliation: Joseph Henry Laboratories of Physics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Mariela D
authors.initials: MD
authors.lastname: Petkova
authors.affiliation: Department of Molecular Biology, Howard Hughes Medical Institute, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Little
authors.affiliation: Joseph Henry Laboratories of Physics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Joseph Henry Laboratories of Physics, Princeton University, Princeton, NJ 08544, USA; Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA. Electronic address: tg2@princeton.edu.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gregor
mesh_terms: D000818:Animals; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D018628:Gene Dosage; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D009866:Oogenesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; C056478:bcd protein, Drosophila