Outside and downstream of the homeobox.
Outside and downstream of the homeobox.
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DOI：
10.1016/s0021-9258(19)36829-2
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发表时间：
1993-10
期刊：
影响因子：
--
通讯作者：
Gerald M. Edelman;Frederick S. Jones
中科院分区：
文献类型：
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作者：
Gerald M. Edelman;Frederick S. Jones
现代生物学的中心有一个重要的谜题，它对生物化学的要求与对遗传学的要求一样。在胚胎发生过程中，细胞如何在身体计划的正确位置形成组织，从而产生物种特征的形状？尽管基因限制组织形成，但 DNA 并不编码供单个细胞遵循的特定时空坐标。那么给定地点的细胞如何在正确的时间到达该位置呢？显然，必须涉及分子线索和精细的调节环路。作为生物化学家，我们希望从形态发生背后的调节生化信号的角度来了解发育。过去 15 年的发育生物学研究已经开始阐明这种调节的本质，并导致了一个值得称为分子胚胎学的领域的出现。同源框基因和细胞粘附分子的分析对该领域做出了特别重要的贡献。在多种动物基因组中发现了许多由同源盒基因编码的转录因子。这些基因产物的区域表达与特定组织和生理学的形成相关。它们的表达以某种方式以位置依赖性方式限制细胞活动，从而导致细胞在三维结构内形成图案。我们还不知道同源框基因及其编码的同源域蛋白是如何实现这一点的。事实上，我们才刚刚开始确定同源盒基因产品的适当靶标。但有一条线索可能有助于解答这个谜题。为了将基因调控转化为动物形式，这些靶标必须能够影响发育过程中相互作用的细胞和组织的机械化学，从而提高细胞粘附分子参与的可能性。最近，同源盒基因产物的假定下游靶基因已被鉴定。有证据支持的候选分子包括细胞粘附分子和底物粘附分子（CAMS 和 SAM）以及各种生长因子。两个分子系统的相互作用，一个是控制位置依赖性转录的同源框基因，另一个是通过粘附调节细胞表面信号事件和细胞力学，可能对于形态发生过程中位置依赖性模式的形成至关重要。
There is an important puzzle at the center of modern biology that is as demanding of biochemistry as it is of genetics. How do cells form tissues at the correct place in the body plan during embryogenesis to yield shapes characteristic of a species? Although genes constrain tissue formation, DNA does not encode specific spatiotemporal coordinates for individual cells to follow. How then can a cell at a given place have reached that location at the right time? Obviously, molecular cues and refined regulatory loops must be involved. As biochemists, we would like to understand development in terms of the regulatory biochemical signals that underlie morphogenesis. Research in developmental biology during the last 15 years has begun to clarify the nature of this regulation and has led to the emergence of a field that deserves to be called molecular embryology. Analyses of homeobox genes and of cell adhesion molecules have made particularly significant contributions to this field. Scores of transcription factors encoded by homeobox genes have been discovered in a wide variety of animal genomes. The regional expression of these gene products is correlated with the formation of specific tissues and physiology. Somehow their expression constrains cellular activity in a place-dependent fashion, resulting in the patterning of cells within three-dimensional structures. We do not yet know how homeobox genes and their encoded homeodomain proteins carry this out. Indeed, we are just beginning to identify appropriate targets of homeobox gene products. But there is a clue that may help answer the puzzle. To convert genetic regulation into animal form, such targets must be able to affect the mechanochemistry of interacting cells and tissues during development, raising the possibility that cell adhesion molecules may be involved.Recently putative downstream target genes for homeobox gene products have been identified. The candidates for which evidence exists include cell adhesion and substrate adhesion molecules (CAMS’and SAMs) as well as various growth factors. Interaction of two molecular systems, one for homeobox genes controlling place-dependent transcription and another modulating cell surface signaling events and cellular mechanics through adhesion, may be essential for place-dependent pattern formation during morphogenesis.