ZFIN ID: ZDB-PUB-170709-3
Clock1a affects mesoderm development and primitive hematopoiesis by regulating Nodal-Smad3 signalings in the zebrafish embryo
Bian, S.S., Zheng, X.L., Sun, H.Q., Chen, J.H., Lu, Y.L., Liu, Y.Q., Tao, D.C., Ma, Y.X.
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:
  • Animals
  • DNA-Binding Proteins/antagonists & inhibitors
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Embryo, Nonmammalian/abnormalities
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Embryonic Development*/drug effects
  • Gene Expression Regulation, Developmental
  • HEK293 Cells
  • Hematopoiesis/drug effects
  • Humans
  • In Situ Hybridization
  • Luminescent Proteins/genetics
  • Luminescent Proteins/metabolism
  • Mesoderm/abnormalities
  • Mesoderm/cytology
  • Mesoderm/drug effects
  • Mesoderm/metabolism*
  • Microinjections
  • Microscopy, Fluorescence
  • Morpholinos/pharmacology
  • Mutation
  • Nodal Protein/agonists*
  • Nodal Protein/genetics
  • Nodal Protein/metabolism
  • Recombinant Fusion Proteins/chemistry
  • Recombinant Fusion Proteins/metabolism
  • Recombinant Proteins/chemistry
  • Recombinant Proteins/metabolism
  • Response Elements/drug effects
  • Signal Transduction*/drug effects
  • Smad3 Protein/agonists*
  • Smad3 Protein/antagonists & inhibitors
  • Smad3 Protein/genetics
  • Smad3 Protein/metabolism
  • Zebrafish*
  • Zebrafish Proteins/agonists*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 28687631 Full text @ J. Biol. Chem.
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.