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An evo-devo approach to thyroid hormones in cerebral and cerebellar cortical development: etiological implications for autism.

ABSTRACT: The morphological alterations of cortical lamination observed in mouse models of developmental hypothyroidism prompted the recognition that these experimental changes resembled the brain lesions of children with autism; this led to recent studies showing that maternal thyroid hormone deficiency increases fourfold the risk of autism spectrum disorders (ASD), offering for the first time the possibility of prevention of some forms of ASD. For ethical reasons, the role of thyroid hormones on brain development is currently studied using animal models, usually mice and rats. Although mammals have in common many basic developmental principles regulating brain development, as well as fundamental basic mechanisms that are controlled by similar metabolic pathway activated genes, there are also important differences. For instance, the rodent cerebral cortex is basically a primary cortex, whereas the primary sensory areas in humans account for a very small surface in the cerebral cortex when compared to the associative and frontal areas that are more extensive. Associative and frontal areas in humans are involved in many neurological disorders, including ASD, attention deficit-hyperactive disorder, and dyslexia, among others. Therefore, an evo-devo approach to neocortical evolution among species is fundamental to understand not only the role of thyroid hormones and environmental thyroid disruptors on evolution, development, and organization of the cerebral cortex in mammals but also their role in neurological diseases associated to thyroid dysfunction.

SUBMITTER: Berbel P

PROVIDER: S-EPMC4158880 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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An evo-devo approach to thyroid hormones in cerebral and cerebellar cortical development: etiological implications for autism.

Berbel Pere P Navarro Daniela D Román Gustavo C GC

Frontiers in endocrinology 20140909

The morphological alterations of cortical lamination observed in mouse models of developmental hypothyroidism prompted the recognition that these experimental changes resembled the brain lesions of children with autism; this led to recent studies showing that maternal thyroid hormone deficiency increases fourfold the risk of autism spectrum disorders (ASD), offering for the first time the possibility of prevention of some forms of ASD. For ethical reasons, the role of thyroid hormones on brain d ...[more]

PMID: 25250016

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Project description:BackgroundUnderstanding how genes change during evolution to direct the development of diverse body plans is a major goal of the evo-devo field. Achieving this will require the establishment of new model systems that represent key points in phylogeny. These new model systems must be amenable to laboratory culture, and molecular and functional approaches should be feasible. To date, studies of insects have been best represented by the model system Drosophila melanogaster. Given the enormous diversity represented by insect taxa, comparative studies within this clade will provide a wealth of information about the evolutionary potential and trajectories of alternative developmental strategies.ResultsHere we established the beetle Dermestes maculatus, a member of the speciose clade Coleoptera, as a new insect model system. We have maintained a continuously breeding culture in the lab and documented Dermestes maculatus embryogenesis using nuclear and phalloidin staining. Anterior segments are specified during the blastoderm stage before gastrulation, and posterior segments are added sequentially during germ band elongation. We isolated and studied the expression and function of the pair-rule segmentation gene paired in Dermestes maculatus. In this species, paired is expressed in stripes during both blastoderm and germ band stages: four primary stripes arise prior to gastrulation, confirming an intermediate-germ mode of development for this species. As in other insects, these primary stripes then split into secondary stripes. To study gene function, we established both embryonic and parental RNAi. Knockdown of Dmac-paired with either method resulted in pair-rule-like segmentation defects, including loss of Engrailed expression in alternate stripes.ConclusionsThese studies establish basic approaches necessary to use Dermestes maculatus as a model system. Methods are now available for use of this intermediate-germ insect for future studies of the evolution of regulatory networks controlling insect segmentation, as well as of other processes in development and homeostasis. Consistent with the role of paired in long-germ Drosophila and shorter-germ Tribolium, paired functions as a pair-rule segmentation gene in Dermestes maculatus. Thus, paired retains pair-rule function in insects with different modes of segment addition.

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An evo-devo approach to thyroid hormones in cerebral and cerebellar cortical development: etiological implications for autism.

Publications

An evo-devo approach to thyroid hormones in cerebral and cerebellar cortical development: etiological implications for autism.

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