Korean Circ J.  2017 Mar;47(2):160-167. 10.4070/kcj.2016.0280.

Spatial Allocation and Specification of Cardiomyocytes during Zebrafish Embryogenesis

• Fukui H
• Chiba A
• Miyazaki T
• Takano H
• Ishikawa H
• Omori T
• Mochiuzki

• KMID: 2377452
• DOI: http://doi.org/10.4070/kcj.2016.0280

Abstract

Incomplete development and severe malformation of the heart result in miscarriage of embryos because of its malfunction as a pump for circulation. During cardiogenesis, development of the heart is precisely coordinated by the genetically-primed program that is revealed by the sequential expression of transcription factors. It is important to investigate how spatial allocation of the heart containing cardiomyocytes and other mesoderm-derived cells is determined. In addition, the molecular mechanism underlying cardiomyocyte differentiation still remains elusive. The location of ectoderm-, mesoderm-, and endoderm-derived organs is determined by their initial allocation and subsequent mutual cell-cell interactions or paracrine-based regulation. In the present work, we provide an overview of cardiac development controlled by the germ layers and discuss the points that should be uncovered in future for understanding cardiogenesis.

Keyword

Embryo development; Cardiac differentiation; Cardiomyocyte; Cardiac progenitor cell; Cilia

MeSH Terms

Abortion, Spontaneous
Cilia
Embryonic Development*
Embryonic Structures
Female
Germ Layers
Heart
Humans
Myocytes, Cardiac*
Pregnancy
Transcription Factors
Zebrafish*
Transcription Factors

Figure

• 

  Fig. 1 Mechanisms underlying left-right axis determination. DFCs derived from the endoderm form the KV. The rotation of cilia promotes unidirectional flow in the KV, thereby inducing left-sided specific nodal-related genes. These gene expressions determine the allocation of LPM-derived organs as well as that of the endoderm-derived organs. DFCs: dorsal forerunner cells, KV: Kupffer's vesicle, LPM: lateral plate mesoderm, R: right, L: left.

• 

  Fig. 2 DFC migration. DFCs can be marked by sox17 promoter activity. The sequential images of Tg (sox17:gfp) from the bud stage (0 h). The elapsed time is indicated at the left top of each image. Arrow heads indicate the DFCs. Arrow indicate the KV. DFC: dorsal forerunner cell, KV: Kupffer's vesicle.

• 

  Fig. 3 The Kupffer's vesicle. A Tg (sox1:gfp) embryo at 6 somite stage was immunostained with anti-acetylated tubulin (red). Note that GFP-positive cells are KV-constituting cells with cilia positive for acetylated tubulin. GFP: green fluorescent protein, KV: Kupffer's vesicle.

• 

  Fig. 4 CPC migration towards the midline. The fate-determined CPCs located in bilateral LPM move towards the midline to form cardiac cone around 22 hfp (upper panel). They migrate in the region sandwiched by the endoderm and the YSL. hpf: hours post fertilization, CPC: cardiac precursor cell, LPM: lateral plate mesoderm, YSL: yolk syncytial layer.

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  Fig. 5 S1P-regulated proper endoderm formation that is required for CPC migration. S1P released from the YSL activate S1P2 receptor expressed in the endodermal cells. The activated S1P2-mediated signal, then, promotes the translocation of Yap1 into the nucleus. Yap1-promoted Ctgfa. Ctgfa maintains the endoderm that becomes the foothold for CPC migration. S1P: sphingosine 1-phosphate, CPC: cardiac precursor cell, YSL: yolk syncytial layer, Ctgfa: connective tissue growth factor gene A.

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