Modular development of the teleost trunk along the dorsoventral axis and zic1/zic4 as selector genes in the dorsal module

Abstract

SUMMARYTeleost fish exhibit remarkable diversity in morphology, such as fins and coloration, particularly on the dorsal side. These structures are evolutionary adaptive because their back is highly visible to other individuals. However, owing to the late phenotypic appearance (from larva to adult) and lack of appropriate mutants, the genetic mechanisms that regulate these dorsoventrally asymmetric external patterns are largely unknown. To address this, we have analyzed the spontaneous medaka mutant Double anal fin (Da), which exhibits a mirror-image duplication of the ventral half across the lateral midline from larva to adult. Da is an enhancer mutant for zic1 and zic4 in which their expression in dorsal somites is lost. We show that the dorsoventral polarity in Da somites is lost and then demonstrate using transplantation techniques that somites and their derived tissues globally determine the multiple dorsal-specific characteristics of the body (fin morphology and pigmentation) from embryo to adult. Intriguingly, the zic1/zic4 expression in the wild type persists throughout life in the dorsal parts of somite derivatives, i.e. the myotome, dermis and vertebrae, forming a broad dorsal domain in the trunk. Comparative analysis further implies a central role for zic1/zic4 in morphological diversification of the teleost body. Taken together, we propose that the teleost trunk consists of dorsal/ventral developmental modules and that zic1/zic4 in somites function as selector genes in the dorsal module to regulate multiple dorsal morphologies.

Large hypomethylated domains serve as strong repressive machinery for key developmental genes in vertebrates

“…Given that HMD size correlates with transcriptional repression level, this HMD shortening might promote zic1/zic4 expression. To examine when this HMD shortening occurs during development, we additionally investigated the DNA methylation pattern in dorsal and ventral myotome at the hatching stage, a stage when the dorsal-specific expression of zic1/zic4 is already induced (Kawanishi et al, 2013). As expected, ChIP-qPCR revealed that the pattern of active and repressive histone modifications was already established in the dorsal and ventral myotome by the hatching stage ( Fig.…”

“…We focused on the zic1 and zic4 (zic1/zic4) genes because they have a particularly large K27HMD (26 kb) in medaka blastula embryos (Fig. 5A) and their function has been extensively studied in medaka (Kawanishi et al, 2013;Moriyama et al, 2012). zic1/ zic4, organized head-to-head with a small intergenic sequence (∼3.4 kb), encode zinc-finger transcription factors and function in the neuronal development and specification of dorsal fate in the trunk (Kawanishi et al, 2013;Merzdorf, 2007).…”

“…5A) and their function has been extensively studied in medaka (Kawanishi et al, 2013;Moriyama et al, 2012). zic1/ zic4, organized head-to-head with a small intergenic sequence (∼3.4 kb), encode zinc-finger transcription factors and function in the neuronal development and specification of dorsal fate in the trunk (Kawanishi et al, 2013;Merzdorf, 2007). They are thought to share cis-regulatory elements and thus their expression is nearly identical.…”

“…It is known that their expression is activated by secreted factors during embryogenesis, and is autonomously maintained throughout life in the dorsal parts of somite derivatives, i.e. the myotome, dermis and vertebrae (Kawanishi et al, 2013). Thus, these genes served as a good example with which to analyze the change in epigenetic states of key developmental genes from embryo to adult.…”

Selection of Sensitive Methylation Markers for the Detection of Non-small Cell Lung Cancer

“…All of these five genes can act as transcription factors to affect early embryo development. For instances, Dmrta2 in mice is essential in the early development of the telencephalon via the formation of the cortical hem and maintaining of neural progenitors [39]; homeobox genes HOXA9 and HOXA7 spatially and temporally regulate morphogenesis and differentiation during embryonic development [40]; homeobox gene SIX3 provides necessary instructions for the formation of the forebrain and eye development [41]; ZIC4 has been proposed to regulate lateemerging characteristics in the dorsal surface with ZIC1 [42]. Due to their important roles in embryo development, methylation of these genes could affect important cellular functions and eventually promote tumorigenesis.…”