As mentioned above, the importance for developmental toxicology of the discovery of extensive conservation of components and processes among seemingly disparate animals is the conclusion that the study or testing of toxicants in model animals can provide relevant information about humans, as long as the extrapolation is done within conserved responses, of which there are many.

Organogenesis

Organs are usually defined as containing two or more tissues, each tissue containing differing cell types and cell functions, coordinated in a higher level of organization and function than the independent tissues. Second to the organism’s overall body organization, organs are the most complex level of organization of cells. Organogenesis is the organ-forming phase of embryonic development. It begins once the basic anteroposterior and dorsoventral organization of the embryo is established by gastrulation and neurulation. During organogenesis, cytodifferentiation takes place, and then the organ begins to function.

A fundamental question about organogenesis concerns the means by which the different parts of the organ are brought into complex alignment and integrated function. In the first half of the twentieth century, organ formation was described in detail by light microscopy, and the inductive interactions of different cell groups involved in organ formation were revealed by experimental analysis. In general, the different tissues of the organ were not found to form independently and then come together in perfect apposition. Rather, tissues that are nearby as a result of extensive movement during gastrulation and neurulation interact with each other and also with surrounding tissues. Combinations of signals establish positional identity and initiate the progressive delineation of organ-specific gene activations. Thus, it is not necessary that all participants in early organogenesis have position and cell-type specific information. Cell signaling operates throughout organogenesis. Recently, the local signals and responses have been identified in several kinds of organogenesis, the responses often being experimentally proven by using “marker” or “reporter” genes activated at various stages of the process and visualized by staining specific mRNAs by in situ hybridization. Extensive molecular descriptions and cellular and genetic analyses have defined key regulatory pathways that facilitate the development of many vertebrate systems, including the following:

  • Neural tube: regionalization of forebrain, midbrain, hindbrain, and spinal cord (for reviews, see Wassef and Joyner 1997; Brewster and Dahmane 1999; Dasen and Rosenfeld 1999; Veraksa et al. 2000).

  • Neural tube: dorso-ventral organization of brain and spinal cord (for reviews, see Edlund and Jessell 1999; Lee and Jessell 1999).

  • Sensory systems: optic vesicle and eye, otic vesicle and inner ear, and olfactory epithelium (for reviews, see Fekete 1999; Holme and Steel 1999; Kraus and Lufkin 1999; McAvoy et al. 1999).



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