PUBLICATION
Clock1a affects mesoderm development and primitive hematopoiesis by regulating Nodal-Smad3 signalings in the zebrafish embryo
- Authors
- Bian, S.S., Zheng, X.L., Sun, H.Q., Chen, J.H., Lu, Y.L., Liu, Y.Q., Tao, D.C., Ma, Y.X.
- ID
- ZDB-PUB-170709-3
- Date
- 2017
- Source
- The Journal of biological chemistry 292(34): 14165-14175 (Journal)
- Registered Authors
- Ma, Yongxin
- Keywords
- SMAD transcription factor, clock gene, hematopoiesis, mesoderm, nodal, transcription promoter, zebrafish
- MeSH Terms
-
- Smad3 Protein/agonists*
- Smad3 Protein/antagonists & inhibitors
- Smad3 Protein/genetics
- Smad3 Protein/metabolism
- Hematopoiesis/drug effects
- In Situ Hybridization
- Recombinant Fusion Proteins/chemistry
- Recombinant Fusion Proteins/metabolism
- Embryo, Nonmammalian/abnormalities
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/drug effects
- Embryo, Nonmammalian/metabolism
- Zebrafish Proteins/agonists*
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- DNA-Binding Proteins/antagonists & inhibitors
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism*
- Mesoderm/abnormalities
- Mesoderm/cytology
- Mesoderm/drug effects
- Mesoderm/metabolism*
- Microinjections
- Embryonic Development*/drug effects
- Zebrafish*
- HEK293 Cells
- Luminescent Proteins/genetics
- Luminescent Proteins/metabolism
- Animals
- Signal Transduction*/drug effects
- Mutation
- Recombinant Proteins/chemistry
- Recombinant Proteins/metabolism
- Nodal Protein/agonists*
- Nodal Protein/genetics
- Nodal Protein/metabolism
- Microscopy, Fluorescence
- Response Elements/drug effects
- Humans
- Gene Expression Regulation, Developmental
- Morpholinos/pharmacology
- PubMed
- 28687631 Full text @ J. Biol. Chem.
Citation
Bian, S.S., Zheng, X.L., Sun, H.Q., Chen, J.H., Lu, Y.L., Liu, Y.Q., Tao, D.C., Ma, Y.X. (2017) Clock1a affects mesoderm development and primitive hematopoiesis by regulating Nodal-Smad3 signalings in the zebrafish embryo. The Journal of biological chemistry. 292(34):14165-14175.
Abstract
Circadian clock and Smad2/3/4-mediated Nodal signaling regulate multiple physiological and pathological processes. However, it remains unknown whether Clock directly cross-talks with Nodal signaling and how this would regulate embryonic development. Here we show that Clock1a coordinated mesoderm development and primitive hematopoiesis in zebrafish embryos by directly up-regulating Nodal-Smad3 signaling. We found that Clock1a is expressed both maternally and zygotically throughout early zebrafish development. We also noted that Clock1a alterations produce embryonic defects with shortened body length, lack of the ventral tail fin, or partial defect of the eyes. Clock1a regulates the expression of the mesodermal markers ntl, gsc, and eve1 and of the hematopoietic markers scl, lmo2, and fli1a Biochemical analyses revealed that Clock1a stimulates Nodal signaling by increasing expression of Smad2/3/4. Mechanistically, Clock1a activates the smad3a promoter via its E-box1 element (CAGATG). Taken together, these findings provide mechanistic insight into the role of Clock1a in the regulation of mesoderm development and primitive hematopoiesis via modulation of Nodal-Smad3 signaling and indicate that Smad3a is directly controlled by the circadian clock in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping