NOTO

Last update 08 May 2025

Basic Info

Synonyms

Homeobox protein notochord, NOTO, notochord homeobox

Introduction

Transcription regulator acting downstream of both FOXA2 and Brachyury (T) during notochord development. Required for node morphogenesis. Is essential for cilia formation in the posterior notochord (PNC) and for left-right patterning; acts upstream of FOXJ1 and RFX3 in this process and is required for the expression of various components important for axonemal assembly and function. Plays a role in regulating axial versus paraxial cell fate. Activates the transcription of ciliary proteins C11orf97 homolog, FAM183B and SPACA9 in the embryonic ventral node (By similarity).

100 Clinical Results associated with NOTO

100 Translational Medicine associated with NOTO

0 Patents (Medical) associated with NOTO

Literatures (Medical) associated with NOTO

01 May 2023·Ecotoxicology and environmental safety

Resveratrol ameliorates penconazole-induced cardiotoxicity by inhibition of oxidative stress and apoptosis in zebrafish larvae.

Article

Author: Zhu, Haiyan ; Zhou, Wendi ; Jiang, Xue ; Liu, Jin ; Wang, Jie ; Hu, Jian ; Sun, Xingzhen

Penconazole (PEN) is a typical systemic triazole fungicide with cardiac toxic effects. Resveratrol (RES) is a natural polyphenolic phytochemical with antioxidation properties. This study aimed to investigate if RES could protect against PEN-induced cardiotoxicity and to determine the underlying mechanisms. Zebrafish embryos were exposed to 0, 0.5, 1 and 2 mg/L of PEN from 4 to 96 h post fertilization (hpf) and cardiac developmental toxicity was assessed. Our results showed that PEN decreased hatching rate, survival rate, heart rate and body length, with increased malformation rate and spontaneous movement. PEN induced pericardial edema and abnormal cardiac structure in myl7:egfp transgenic zebrafish, as well as downregulation of cardiac development related genes (nkx2.5, tbx2.5, gata4, noto, and vmhc). In addition, PEN elevated oxidative stress via reactive oxygen species (ROS) accumulation and triggered cardiomyocytic apoptosis by upregulation of p53, bcl-2, bax and caspase 3. These adverse outcomes were counteracted by RES, indicating that RES ameliorated PEN-induced cardiotoxicity by inhibiting oxidative stress and apoptosis in zebrafish. Taken together, this study revealed the important role of oxidative stress in PEN-induced cardiotoxicity and identified dietary RES supplementation as a novel strategy to mitigate its toxicity.

23 Feb 2023·Nature

Dissecting cell identity via network inference and in silico gene perturbation

Article

Author: Stringa, Blerta ; Morris, Samantha A ; Jindal, Kunal ; Kamimoto, Kenji ; Hoffmann, Christy M ; Solnica-Krezel, Lilianna

AbstractCell identity is governed by the complex regulation of gene expression, represented as gene-regulatory networks1. Here we use gene-regulatory networks inferred from single-cell multi-omics data to perform in silico transcription factor perturbations, simulating the consequent changes in cell identity using only unperturbed wild-type data. We apply this machine-learning-based approach, CellOracle, to well-established paradigms—mouse and human haematopoiesis, and zebrafish embryogenesis—and we correctly model reported changes in phenotype that occur as a result of transcription factor perturbation. Through systematic in silico transcription factor perturbation in the developing zebrafish, we simulate and experimentally validate a previously unreported phenotype that results from the loss of noto, an established notochord regulator. Furthermore, we identify an axial mesoderm regulator, lhx1a. Together, these results show that CellOracle can be used to analyse the regulation of cell identity by transcription factors, and can provide mechanistic insights into development and differentiation.

15 Dec 2021·DevelopmentQ2 · BIOLOGY

Molecular mechanisms of embryonic tail development in the self-fertilizing mangrove killifish Kryptolebias marmoratus

Q2 · BIOLOGY

Article

Author: Saud, Hussein A. ; Verbruggen, Bas ; Van Aerle, Ronny ; Lee, Jae-Seong ; Kudoh, Tetsuhiro ; Kim, Jaebum ; Ring, Brian C. ; O'Neill, Paul A. ; Ono, Yosuke

ABSTRACTUsing the self-fertilizing mangrove killifish, we characterized two mutants, shorttail (stl) and balltail (btl). These mutants showed abnormalities in the posterior notochord and muscle development. Taking advantage of a highly inbred isogenic strain of the species, we rapidly identified the mutated genes, noto and msgn1 in the stl and btl mutants, respectively, using a single lane of RNA sequencing without the need of a reference genome or genetic mapping techniques. Next, we confirmed a conserved morphant phenotype in medaka and demonstrate a crucial role of noto and msgn1 in cell sorting between the axial and paraxial part of the tail mesoderm. This novel system could substantially accelerate future small-scale forward-genetic screening and identification of mutations. Therefore, the mangrove killifish could be used as a complementary system alongside existing models for future molecular genetic studies.

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