10779/crick.12666863.v1 Elena De Domenico Elena De Domenico Nick DL Owens Nick DL Owens Ian M Grant Ian M Grant Rosa Gomes-Faria Rosa Gomes-Faria Michael J Gilchrist Michael J Gilchrist Molecular asymmetry in the 8-cell stage Xenopus tropicalis embryo described by single blastomere transcript sequencing The Francis Crick Institute 2020 Cortical rotation Dorsal determinants Molecular asymmetry Polar enrichment of mRNAs Spatial distribution of maternal mRNAs Xenopus tropicalis Animals Blastomeres Body Patterning Female Gene Knockdown Techniques Humans Male Models, Animal Monosaccharide Transport Proteins Mutation RNA, Messenger Transcription, Genetic Xenopus Xenopus Proteins Gilchrist U117597137 AS-ack Developmental Biology 06 Biological Sciences 11 Medical and Health Sciences 2020-07-17 10:59:03 Journal contribution https://crick.figshare.com/articles/journal_contribution/Molecular_asymmetry_in_the_8-cell_stage_Xenopus_tropicalis_embryo_described_by_single_blastomere_transcript_sequencing/12666863 Correct development of the vertebrate body plan requires the early definition of two asymmetric, perpendicular axes. The first axis is established during oocyte maturation, and the second is established by symmetry breaking shortly after fertilization. The physical processes generating the second asymmetric, or dorsal-ventral, axis are well understood, but the specific molecular determinants, presumed to be maternal gene products, are poorly characterized. Whilst enrichment of maternal mRNAs at the animal and vegetal poles in both the oocyte and the early embryo has been studied, little is known about the distribution of maternal mRNAs along either the dorsal-ventral or left-right axes during the early cleavage stages. Here we report an unbiased analysis of the distribution of maternal mRNA on all axes of the Xenopus tropicalis 8-cell stage embryo, based on sequencing of single blastomeres whose positions within the embryo are known. Analysis of pooled data from complete sets of blastomeres from four embryos has identified 908 mRNAs enriched in either the animal or vegetal blastomeres, of which 793 are not previously reported as enriched. In contrast, we find no evidence for asymmetric distribution along either the dorsal-ventral or left-right axes. We confirm that animal pole enrichment is on average distinctly lower than vegetal pole enrichment, and that considerable variation is found between reported enrichment levels in different studies. We use publicly available data to show that there is a significant association between genes with human disease annotation and enrichment at the animal pole. Mutations in the human ortholog of the most animally enriched novel gene, Slc35d1, are causative for Schneckenbecken dysplasia, and we show that a similar phenotype is produced by depletion of the orthologous protein in Xenopus embryos.