Recent progress in the technique of next generation sequencing has been remarkable in uncovering species‐specific developmental mechanisms even in non‐model animals. In this special issue, we focus on how morphological diversity or species‐specific unique morphology was evolutionarily brought about by acquisition of novel enhancer functions, which has been elucidated using analyses of developmental biology and whole genome sequences of various organisms mostly determined by next generation sequencing.

In the past, there was debate about what regions in the genome were responsible for morphological differences among species. Many cases were reported of such genetic causes in coding regions of genes; however, this bias was partly due to the technical difficulty in analyzing noncoding regions. Variations in nucleotide sequences of coding regions and gene copy numbers were well documented because it is easy to establish their association with functions. In contrast, it is very difficult to infer the effects of mutations in gene control regions only from the sequence information, and therefore such effects have been paid less attention or undervalued for a long time. From the early 2000s, the idea that the evolution of cis ‐regulatory sequences in non‐coding DNA regions, especially enhancers that upregulate gene expression, contributed to morphological diversification, has become popular (Carroll, 2005; Stern & Orgogozo, 2008). Although alterations of coding regions of developmental genes often disrupt their essential functions, those of enhancers result in addition or deletion of activities with preserving their essential functions. It is also argued that, when considering the structure of the gene regulatory network, evolution of binding sequences of transcription factors on the DNA is much easier than that of DNA binding properties of transcription factors. A growing body of experimental EvoDevo research has now been showing that various types of morphological diversity are explained by differences in the regulatory regions of genes of interest.

We asked researchers to write review articles covering a wide range of animals, from invertebrates to vertebrates. The following 10 researchers or groups contributed to this special issue, in which most review articles were based on their latest and remarkable accomplishments.

Kuroiwa (2020) gave an overview of the emerging themes as a result of recent technological innovations in analyzing the molecular basis of morphological diversity during evolution. Koshikawa (2020) reviewed recent studies on the evolution of pigmentation patterns in the Drosophila wing as an advantageous model for studying the evolutionary mechanism and parallel evolution of traits. Yasuoka (2020) used functional analysis of the cis ‐regulatory module (CRM) of amphioxus as an example to explain how conservation and variability of CRM functions contributed to the evolution of gene regulatory networks in chordates. Liu and Satou (2020) clarified and discussed how the genetic circuit is evolutionarily conserved between ascidians and vertebrates and how genetic programs regulate the regionalization of ectoderm‐derived tissues in ascidian embryogenesis. Enny, Flaherty, Mori, Turner, and Nakamura (2020) described the evolutionary history of fins of fish, the mechanism of fin development, and the basis of evolution of paired fins and also described possible developmental constraints on fin evolution. Onimaru (2020) discussed the evolutionary origin of conserved non‐coding elements (CNEs) that function as tissue‐specific developmental enhancers, particularly focusing on the water‐to‐land transition during vertebrate evolution. Amano (2020) described how versatile expression patterns of the Shh gene are controlled by multiple cis ‐regulatory elements and how vertebrate lineages acquired distinct morphological features. Suzuki and Ochi (2020) summarized their recent study of injury/regeneration‐related enhancers, named "regeneration signal‐response enhancers (RSREs)," and discussed the mechanism of their activation. Sumiyama and Tanave (2020) introduced the latest findings on the regulation of three Dlx "bigene" clusters from the point of view of cis ‐regulatory motifs, TAD (Topologically Associating Domain) boundaries, CTCF loops, and distal enhancer landscapes. Taking the regulatory mechanism of Hox gene expression as an example, Saito and Suzuki (2020) discussed how the diversity of skeletal patterns among vertebrate species was brought about.

Thus, in this special issue, we introduce and share the latest findings on how the molecular mechanisms underlying morphological diversity of organisms has been elucidated through the studies of gene regulatory mechanisms. This special issue was based on the symposium “Enhancer function explaining morphological diversity” held on May 17th, 2019, in the 52nd Annual Meeting of the Japanese Society of Developmental Biologists, in Osaka, Japan.

即使在非模型动物中，下一代测序技术的最新进展在发现特定物种的发育机制方面也非常引人注目。在本期特刊中，我们重点介绍如何通过获取新的增强子功能来进化带来形态多样性或特定物种的独特形态，这一点已通过分析发育生物学和各种生物的全基因组序列（主要由下一代测序确定）得以阐明。

过去，关于基因组中哪些区域导致物种间形态差异的争论一直存在。据报道，在基因编码区有许多这样的遗传原因。但是，这种偏差部分是由于分析非编码区域的技术难度。编码区核苷酸序列和基因拷贝数的变异已得到充分记录，因为很容易确定它们与功能的关联。相反，仅从序列信息推断基因控制区中的突变的影响是非常困难的，因此长期以来，这种影响很少受到关注或被低估了。从2000年代初期开始，顺式的进化非编码DNA区域的调控序列，特别是上调基因表达的增强子，促进了形态的多样化，已变得很流行（Carroll，  2005 ; Stern＆Orgogozo，  2008）。尽管发育基因编码区的改变通常会破坏其基本功能，但增强子的改变会导致保留原有功能的活动增加或删除。也有人认为，当考虑基因调控网络的结构时，DNA上转录因子结合序列的进化要比转录因子的DNA结合特性容易得多。现在，越来越多的实验性EvoDevo研究表明，各种类型的形态多样性可以通过关注基因的调控区域的差异来解释。

我们要求研究人员撰写评论文章，涵盖从无脊椎动物到脊椎动物的各种动物。以下10个研究人员或小组对此特刊做出了贡献，其中大多数评论文章都是基于他们的最新成就和非凡成就。

Kuroiwa（2020）概述了新兴主题，这些主题是最近的技术创新，用于分析进化过程中形态多样性的分子基础。Koshikawa（2020）综述了果蝇翅膀上色素沉着模式演变的最新研究，以此作为研究性状进化机制和平行进化的有利模型。Yasuoka（2020）以安非他命的顺式调控模块（CRM）的功能分析为例，解释了CRM功能的保守性和可变性如何促进了脊索动物中基因调控网络的进化。刘和头（2020）阐明并讨论了海鞘和脊椎动物之间遗传回路如何在进化上保守，以及遗传程序如何调控海鞘胚胎发生中外胚层组织的区域化。Enny，Flaherty，Mori，Turner和Nakamura（2020年）描述了鱼鳍的进化历史，鳍的发育机理以及成对鳍的进化基础，还描述了鳍进化的可能发展制约因素。Onimaru（2020）讨论了保守非编码元件（CNE ）的进化起源，它们起组织特定的发育促进剂的作用，尤其着重于脊椎动物进化过程中的水-陆过渡。天野（2020）描述了如何通用的表达模式。Shh基因受多种顺式调控元件的控制，以及脊椎动物谱系如何获得独特的形态特征。Suzuki和Ochi（2020）总结了他们最近对损伤/再生相关增强子的研究，命名为“再生信号响应增强子（RSRE）”，并讨论了其激活机制。住山和Tanave（2020）介绍的三个调节的最新发现DLX “bigene”簇从视图的点顺-regulatory基序，TAD（拓扑缔域）边界，CTCF循环和远端增强子景观。以Sax和Suzuki为例，以Hox基因表达的调控机制为例（2020年）讨论了脊椎动物物种之间骨骼模式的多样性是如何产生的。

因此，在本期特刊中，我们介绍并分享了有关如何通过基因调控机制研究阐明生物形态多样性的分子机制的最新发现。本期特刊基于2019年5月17日在日本大阪举行的日本发展生物学家学会第52届年会上举行的研讨会“增强功能，解释形态多样性”。