Research

Evolution is an often surprisingly fast process that results in new adaptations, but also is the mechanism for the origin of novel species. Genetic variation and the resulting changes in an organism’s characteristics are the raw material for selection to act on, which might allow for the evolution of adaptations. My study organisms are cichlid fish, a famous textbook example of exuberant color diversity and record-breaking rates at which new species arise, chosen as a means for understanding the molecular, cellular and developmental mechanisms that drive phenotypic diversity that Charles Darwin already talked about in the “Origin of Species”: “From so simple a beginning, endless forms most beautiful and most wonderful have been, and are being, evolved”.

Closing the genotype-phenotype gap – How genetic changes lead to evolutionary diversification

Cichlid fishes are an excellent model system for understanding phenotypic diversification from a genomic standpoint. They are a famous example of explosive adaptive radiation — in less than a few million years over 1,200 species evolved in the three East African Lakes Victoria, Tanganyika, and Malawi. This astonishing rate of diversification makes them a suitable family of vertebrates to investigate the genetic changes associated with diversification in coloration. Coloration is undoubtedly one of the traits that strongly affected the adaptation and exceptional rate of speciation. Cichlids have been described as a "natural mutagenesis screen" that allows researchers to screen for genes underlying these phenotypes. This analogy stems from the observation that this exceptional degree of phenotypic diversification is associated with a very low degree of genetic diversification. As a result of recent divergence, many cichlids can be hybridized permitting Quantitative Loci Mapping (QTL) studies. Therefore, they are an exceptional model system to study genotype-phenotype relationships. I focus particularly on understanding the genetic basis of color patterns as horizontal stripe and vertical bar patterns.

Tinkering with gene regulation – How regulatory evolution drives phenotypic diversification

Gene regulatory changes generate phenotypic changes very fast, through orchestrating changes in cellular proliferation, cell identity and cell-cell communication. Once dismissed as ‘junk DNA’, the importance of the role of non-coding DNA has only begun to be appreciated recently – also through unbiased approaches to map regulatory elements and the expanding toolset in non-model organisms. It has been suggested that changes in regulatory networks constitute a major catalyst for phenotypic evolution by controlling gene expression patterns and levels, although its relative importance compared to typical evolutionary changes in exons was debated until recently. Using sequencing methods (RNA-seq, ChIP-seq, ATAC-seq) as well as genome-editing (CRISPR-Cas) and transgenic methods (Tol2) I aim to understand how regulatory changes drive phenotypic diversification,

References:
Kratochwil CF, Liang Y, Gerwin J, Woltering JM, Urban S, Henning F, Machado-Schiaffino G, Hulsey CD, and Meyer A. 2018. Agouti-related peptide 2 facilitates convergent evolution of stripe patterns across cichlid fish radiations. Science 362:457–460.
Kratochwil CF*, Sefton MS*, Liang Y, and Meyer A (2017). Tol2 transposon-mediated transgenesis in the Midas cichlid (Amphilophus citrinellus) — towards understanding gene function and regulatory evolution in an ecological model system for rapid phenotypic diversification. BMC Developmental Biology 17: 15 Link
Kratochwil CF*, Geissler L*, Irisarri I*, and Meyer A (2015). Molecular evolution of the neural crest regulatory network in ray-finned fish. Genome Biology and Evolution 7 (11), 3033-3046. Link
Kratochwil CF and Meyer A (2015). Evolution: Tinkering within gene regulatory landscapes. Current Biology 25 (7) R185-R288 Link
Kratochwil CF and Meyer A (2015). Closing the genotype–phenotype gap: Emerging technologies for evolutionary genetics in ecological model vertebrate systems. BioEssays 37 (2), 213-226. Link

How are color patterns generated - The roles of cellular dynamics and development

Knowing about the underlying genes driving color and color pattern diversification is first step to understand how color and color pattern diversity is generated on a cellular level. The color of a tissue results from the multi-layered organization of pigment cell types with different structural and pigmentary properties. On a macroscopic scale, color patterns arise from spatial differences in pigment cell properties and arrangements to form vertical bars, horizontal stripes, spots or more complex patterns. Ongoing research addresses how these patterns are formed by pigment cells and their interaction and how developmental processes shape these patterns. Furthermore, this allows us to ask what changes occur during the course of evolution.

References:
Kratochwil CF, Liang Y, Gerwin J, Woltering JM, Urban S, Henning F, Machado-Schiaffino G, Hulsey CD, and Meyer A. 2018. Agouti-related peptide 2 facilitates convergent evolution of stripe patterns across cichlid fish radiations. Science 362:457–460.
Kratochwil CF*, Sefton MS*, Liang Y, and Meyer A (2017). Tol2 transposon-mediated transgenesis in the Midas cichlid (Amphilophus citrinellus) — towards understanding gene function and regulatory evolution in an ecological model system for rapid phenotypic diversification. BMC Developmental Biology 17: 15 Link
Kratochwil CF*, Sefton MS*, and Meyer A (2015). Embryonic and larval development in the Midas cichlid fish species flock (Amphilophus spp.): a new evo-devo model for the investigation of adaptive novelties and species differences. BMC Developmental Biology 15: 12 Link
Saemi-Komsari M*, Mousavi-Sabet H*, Kratochwil CF*, Sattari M, Eagderi S, and Meyer A (2018): Early developmental and allometric patterns in the electric yellow cichlid Labidochromis caeruleus. Journal of Fish Biology 92:1888–1 Link

How new species form -A genomic view on speciation and phenotypic diversification

How species form through the build up of local and genome-wide differentiation is still poorly understood. Large genomic data sets allow now to screen for the genomic basis of ecologically relevant phenotypes (i.e. GWAS studies) and to screen for genomic regions under divergent selection. Neotropical Midas cichlids, where a dozen species evolved in less than 20.000 years, provide a complex yet not too complex system to study the genomic changes driving and resulting from speciation.

More information on Midas cichlids and speciation:
Homepage Axel Meyer Lab, University of Konstanz, Germany
Homepage Andreas Kautt, Harvard University, USA

Previous work: How neural (crest) development is shaped by epigenetic and transcriptional regulation

During my early career I became fascinated by the ontogeny of organisms: how, in a a few days, complex cell-types, organs, and behaving organisms develop from a single cell largely instructed by the information encoded in the genome. I found this process particularly remarkable in the brain and in neural crest derived tissues, both giving rise to remarkably diverse cell types and functions. I gained a deeper understanding of the development of several organisms. In zebrafish I studied the formation of the dopaminergic system. Later, during my Ph.D., I adressed the genetic and epigenetic factors that drive and orchestrate the development of one of the most complex neural circuits in the mammalian brain, the cortico- ponto-cerebellar system that connects the forebrain and cerebellum. Similarly, I also contributed to work on understanding the development of the topographically organized whisker-related circuitry and of neural-crest derivatives, as these giving rise to the formation of the external ear.

References:
Kratochwil CF, Maheshwari U, and Rijli FM (2017). The Long Journey of Pontine Nuclei Neurons: From Rhombic lip to Cortico-Ponto-Cerebellar Circuitry. Front. Neural Circuits 11:33 Link
Renier N, Dominici C, Erzurumlu R,, Kratochwil CF, Rijli FM, Gaspar P, and Chedotal A. (2017). A mutant with bilateral whisker to barrel inputs unveils somatosensory mapping rules in the cerebral cortex. eLife 6, e23494 Link
Bechara A, Laumonnerie C, Vilain N, Kratochwil CF, Cankovic V, Maiorano NA, Kirschmann MA, Ducret S, and Rijli F (2015). Hoxa2 selects barelette neuron identity and connectivity in the mouse somatosensory brainstem. Cell Reports. 13 (4), 783-797. Link
Kratochwil CF and Rijli FM (2014): “The Cre/lox system to assess the development of the mouse brain”, Brain development: Methods and Protocols, Methods in Molecular Biology (Simon G. Sprecher ed.), Springer, New York. 1082, 295–313. Link
Di Meglio T*, Kratochwil CF*, Vilain N, Loche A, Vitobello A, Yonehara K, Roska B, Peters AHFM, Wellik D, Ducret S, and Rijli FM (2013). Ezh2 orchestrates topographic tangential migration and connectivity of precerebellar neurons. Science 339 (6116), 204–207. Link
Minoux M, Kratochwil CF, Ducret S, Amin S, Kitazawa T, Kurihara H, Bobola N, Vilain N, and Rijli FM (2013). Mouse Hoxa2 genetic analysis provides a model for microtia and auricle duplication. Development 140 (21), 4386–4397. Link
Kastenhuber E*, Kratochwil CF*, Ryu S*, Schweitzer J, and Driever W (2010). Genetic dissection of dopaminergic and noradrenergic contributions to catecholaminergic tracts in early larval zebrafish. J Comp Neurol 518 (4), 439-458. Link
Tervonen TA*, Louhivuori V*, Sun X, Hokannen M-E, Kratochwil CF, Zebryk P, Castren E, and Castren ML (2009). Aberrant differentiation of glutamatergic cells in neocortex of mouse model for fragile X syndrome. Neurobiol. Dis. 33 (2), 250-259 Link