PMID- 34919801 OWN - NLM STAT- MEDLINE DCOM- 20220210 LR - 20220210 IS - 1878-1551 (Electronic) IS - 1534-5807 (Linking) VI - 57 IP - 1 DP - 2022 Jan 10 TI - Targeted search for scaling genes reveals matrixmetalloproteinase 3 as a scaler of the dorsal-ventral pattern in Xenopus laevis embryos. PG - 95-111.e12 LID - S1534-5807(21)00945-X [pii] LID - 10.1016/j.devcel.2021.11.021 [doi] AB - How embryos scale patterning according to size is still not fully understood. Through in silico screening and analysis of reaction-diffusion systems that could be responsible for scaling, we predicted the existence of genes whose expression is sensitive to embryo size and which regulate the scaling of embryonic patterning. To find these scalers, we identified genes with strongly altered expression in half-size Xenopus laevis embryos compared with full-size siblings at the gastrula stage. Among found genes, we investigated the role of matrix metalloproteinase-3 (mmp3), which was most strongly downregulated in half-size embryos. We show that Mmp3 scales dorsal-ventral patterning by degrading the slowly diffusing embryonic inducers Noggin1 and Noggin2 but preventing cleavage of the more rapidly diffusing inducer Chordin via degradation of a Tolloid-type proteinase. In addition to unraveling the mechanism underlying the scaling of dorsal-ventral patterning, this work provides proof of principal for scalers identification in embryos of other species. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Orlov, Eugeny E AU - Orlov EE AD - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia. FAU - Nesterenko, Alexey M AU - Nesterenko AM AD - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia; Federal Center of Brain Research and Neurotechnology, Federal Medical Biological Agency, 117997 Moscow, Russia. FAU - Korotkova, Daria D AU - Korotkova DD AD - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia; Global Health Institute, School of Life Sciences, EPFL, Lausanne, Switzerland. FAU - Parshina, Elena A AU - Parshina EA AD - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia. FAU - Martynova, Natalia Yu AU - Martynova NY AD - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia; Pirogov Russian National Research Medical University, Moscow, Russia. FAU - Zaraisky, Andrey G AU - Zaraisky AG AD - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia; Pirogov Russian National Research Medical University, Moscow, Russia. Electronic address: azaraisky@yahoo.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211216 PL - United States TA - Dev Cell JT - Developmental cell JID - 101120028 RN - 0 (Bone Morphogenetic Proteins) RN - 0 (Carrier Proteins) RN - 0 (Glycoproteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (NOG2 protein, Xenopus) RN - 0 (Xenopus Proteins) RN - 148294-77-3 (noggin protein) RN - 93586-27-7 (chordin) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Animals MH - Body Patterning/*genetics/physiology MH - Bone Morphogenetic Proteins/metabolism MH - Carrier Proteins/metabolism MH - Cell Size MH - Embryo, Nonmammalian/metabolism MH - Gastrula/metabolism MH - Glycoproteins/metabolism MH - Intercellular Signaling Peptides and Proteins/metabolism MH - Intracellular Signaling Peptides and Proteins/metabolism MH - Matrix Metalloproteinase 3/*metabolism/physiology MH - Organizers, Embryonic/*metabolism MH - Signal Transduction/physiology MH - Xenopus Proteins/metabolism MH - Xenopus laevis/embryology OTO - NOTNLM OT - Chordin OT - Noggin OT - Tolloid OT - embryonic scaling OT - genes regulating scaling OT - mathematical modeling of dorsal-ventral patterning scaling OT - matrix metalloproteinase-3 (Mmp3) OT - notochord OT - somitic mesoderm COIS- Declaration of interests The authors declare no competing interests. EDAT- 2021/12/18 06:00 MHDA- 2022/02/11 06:00 CRDT- 2021/12/17 20:09 PHST- 2020/11/02 00:00 [received] PHST- 2021/05/01 00:00 [revised] PHST- 2021/11/19 00:00 [accepted] PHST- 2021/12/18 06:00 [pubmed] PHST- 2022/02/11 06:00 [medline] PHST- 2021/12/17 20:09 [entrez] AID - S1534-5807(21)00945-X [pii] AID - 10.1016/j.devcel.2021.11.021 [doi] PST - ppublish SO - Dev Cell. 2022 Jan 10;57(1):95-111.e12. doi: 10.1016/j.devcel.2021.11.021. Epub 2021 Dec 16.