RESUMEN
Differences in brain region size among species are thought to arise late in development via adaptive control over neurogenesis, as cells of previously patterned compartments proliferate, die, and/or differentiate into neurons. Here we investigate comparative brain development in ecologically distinct cichlid fishes from Lake Malawi and demonstrate that brains vary among recently evolved lineages because of early patterning. Divergence among rock-dwellers and sand-dwellers in the relative size of the telencephalon versus the thalamus is correlated with gene expression variation in a regulatory circuit (composed of six3, fezf2, shh, irx1b, and wnt1) known from model organisms to specify anterior-posterior (AP) brain polarity and position the shh-positive signaling boundary zona limitans intrathalamica (ZLI) in the forebrain. To confirm that changes in this coexpression network are sufficient to produce the differences we observe, we manipulated WNT signaling in vivo by treating rock-dwelling cichlid embryos with temporally precise doses of LiCl. Chemically treated rock-dwellers develop gene expression patterns, ZLIs, and forebrains distinct from controls and untreated conspecifics, but strongly resembling those of sand-dwellers. Notably, endemic Malawi rock- and sand-dwelling lineages are alternately fixed for an SNP in irx1b, a mediator of WNT signaling required for proper thalamus and ZLI. Together, these natural experiments in neuroanatomy, development, and genomics suggest that evolutionary changes in AP patterning establish ecologically relevant differences in the elaboration of cichlid forebrain compartments. In general, variation in developmental patterning might lay the foundations on which neurogenesis erects diverse brain architectures.
Asunto(s)
Tipificación del Cuerpo , Encéfalo/embriología , Perciformes/anatomía & histología , Perciformes/genética , Animales , Evolución Biológica , Encéfalo/metabolismo , Ecosistema , Proteínas de Peces/genética , Regulación del Desarrollo de la Expresión Génica , Proteínas de Homeodominio/genética , Polimorfismo de Nucleótido Simple , Transducción de Señal , Factores de Transcripción/genética , Proteínas Wnt/metabolismoRESUMEN
Brains develop under the influence of signaling centers that link major dorsal/ventral (DV) and anterior/posterior (AP) axes. Over ontogeny, these 'developmental neuraxes' progress from near global signaling gradients into more localized gene expression domains separated by molecular boundaries. Therefore, developmental changes along a neuraxis can have major consequences across the brain, or more precise effects on a specific structure, depending upon the time during ontogeny in which change occurs. It is well known from mammalian systems how evolution has acted later in development, via differential neurogenesis, to reshape the cortex. Recent studies in fishes show how early changes in DV and AP patterning result in divergence of integrated brain regions that ultimately define visual versus olfactory ecotypes. We explore the generality of this trend and suggest that such early developmental differences integrating brain diversification along the neuraxes may be a common theme in vertebrates. Early differences in brain patterning among species imply that adult variation in sensory function and behavior manifests in the embryo.
Asunto(s)
Encéfalo/embriología , Neurogénesis , Vertebrados/embriología , Animales , Evolución Biológica , Tipificación del Cuerpo , Linaje de la Célula , Inducción Embrionaria , Peces/embriología , Regulación del Desarrollo de la Expresión Génica , Modelos Biológicos , Morfogénesis , Proteínas del Tejido Nervioso/fisiología , Tamaño de los Órganos , Olfato/fisiología , Especificidad de la Especie , Factores de Transcripción/fisiología , Vertebrados/genética , Visión Ocular/fisiología , Proteínas Wnt/fisiologíaRESUMEN
Lake Malawi cichlid fishes exhibit extensive divergence in form and function built from a relatively small number of genetic changes. We compared the genomes of rock- and sand-dwelling species and asked which genetic variants differed among the groups. We found that 96% of differentiated variants reside in non-coding sequence but these non-coding diverged variants are evolutionarily conserved. Genome regions near differentiated variants are enriched for craniofacial, neural and behavioral categories. Following leads from genome sequence, we used rock- vs. sand-species and their hybrids to (i) delineate the push-pull roles of BMP signaling and irx1b in the specification of forebrain territories during gastrulation and (ii) reveal striking context-dependent brain gene expression during adult social behavior. Our results demonstrate how divergent genome sequences can predict differences in key evolutionary traits. We highlight the promise of evolutionary reverse genetics-the inference of phenotypic divergence from unbiased genome sequencing and then empirical validation in natural populations.
Asunto(s)
Conducta Animal , Evolución Biológica , Encéfalo/fisiología , Genoma , Genómica , Animales , Cíclidos/clasificación , Cíclidos/fisiología , Genómica/métodos , Filogenia , TranscriptomaRESUMEN
Interrogating fundamental cell biology principles that govern tissue morphogenesis is critical to better understanding of developmental biology and engineering novel multicellular systems. Recently, functional micro-tissues derived from pluripotent embryonic stem cell (ESC) aggregates have provided novel platforms for experimental investigation; however elucidating the factors directing emergent spatial phenotypic patterns remains a significant challenge. Computational modelling techniques offer a unique complementary approach to probe mechanisms regulating morphogenic processes and provide a wealth of spatio-temporal data, but quantitative analysis of simulations and comparison to experimental data is extremely difficult. Quantitative descriptions of spatial phenomena across multiple systems and scales would enable unprecedented comparisons of computational simulations with experimental systems, thereby leveraging the inherent power of computational methods to interrogate the mechanisms governing emergent properties of multicellular biology. To address these challenges, we developed a portable pattern recognition pipeline consisting of: the conversion of cellular images into networks, extraction of novel features via network analysis, and generation of morphogenic trajectories. This novel methodology enabled the quantitative description of morphogenic pattern trajectories that could be compared across diverse systems: computational modelling of multicellular structures, differentiation of stem cell aggregates, and gastrulation of cichlid fish. Moreover, this method identified novel spatio-temporal features associated with different stages of embryo gastrulation, and elucidated a complex paracrine mechanism capable of explaining spatiotemporal pattern kinetic differences in ESC aggregates of different sizes.