Cdc2-like kinase 2 (Clk2) promotes early neural development in Xenopus embryos

Dev Growth Differ. 2019 Aug;61(6):365-377. doi: 10.1111/dgd.12619. Epub 2019 Jul 3.

Abstract

Neural induction and patterning in vertebrates are regulated during early development by several morphogens, such as bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs). Ventral ectoderm differentiates into epidermis in response to BMPs, whereas BMP signaling is tightly inhibited in the dorsal ectoderm which develops into neural tissues. Here, we show that Cdc2-like kinase 2 (Clk2) promotes early neural development and inhibits epidermis differentiation in Xenopus embryos. clk2 is specifically expressed in neural tissues along the anterior-posterior axis during early Xenopus embryogenesis. When overexpressed in ectodermal explants, Clk2 induces the expression of both anterior and posterior neural marker genes. In agreement with this observation, overexpression of Clk2 in whole embryos expands the neural plate at the expense of epidermal ectoderm. Interestingly, the neural-inducing activity of Clk2 is increased following BMP inhibition and activation of the FGF signaling pathway in ectodermal explants. Clk2 also downregulates the level of p-Smad1/5/8 in cooperation with BMP inhibition, in addition to increasing the level of activated MAPK together with FGF. These results suggest that Clk2 plays a role in early neural development of Xenopus possibly via modulation of morphogen signals such as the BMP and FGF pathways.

Keywords: Xenopus embryogenesis; autism spectrum disorder; axis formation; morphogens; neural development.

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / metabolism
  • Cell Differentiation
  • Cyclin-Dependent Kinase 5 / metabolism*
  • Ectoderm / embryology*
  • Ectoderm / enzymology*
  • Embryo, Nonmammalian / embryology*
  • Embryo, Nonmammalian / enzymology*
  • Fibroblast Growth Factors / metabolism
  • Gene Expression Regulation, Developmental
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Nervous System / embryology*
  • Nervous System / enzymology*
  • Neural Plate / embryology*
  • Neural Plate / enzymology*
  • Signal Transduction
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / embryology*

Substances

  • Bone Morphogenetic Proteins
  • Xenopus Proteins
  • Fibroblast Growth Factors
  • Cyclin-Dependent Kinase 5
  • Mitogen-Activated Protein Kinase Kinases

Associated data

  • GENBANK/NM_001086602.1
  • GENBANK/NM_001011361.1
  • GENBANK/NM_007712.4