Marketa Kaucka Petersen

Please contact Marketa for further information on the project: kaucka@evolbio.mpg.de

The genetic and developmental basis of face formation & the evolution of facial diversity

The head is the most complex and sophisticated part of the vertebrate body, comprising of many cell and tissue types assembled together during a complicated four-dimensional process of morphogenesis. The complex process of head formation is governed by hundreds of genes that control patterning, cell proliferation and specification. The head hosts important and sensitive structures such as the brain and sensory organs including olfactory system (mediates olfaction), inner ear (is responsible for audition), eyes (account for vision) and others. These delicate structures require protection both during embryonic development and postnatally. Such a protection is provided by the skull that has an enormously complex 3D shape. Evolution of the skull has been linked to the evolution of sophisticated nervous system and efficient feeding apparatus that allowed the shift from passive filter-feeding to the predatory lifestyle.

The frontal part of the skull is commonly referred to as “the face”. An immense spectrum of facial shapes is found in the animal kingdom allowing various lifestyles and a broad array of distinct feeding strategies. Humans possess an impressive variability of facial features underlying a person’s individuality and use it for mutual recognition. Facial appearance relies mostly on the geometry of the underlying skeleton. When this geometry is affected, many essential functions including feeding, breathing and communication can be impaired, resulting in the overall decrease in the fitness or well-being.

Two types of stiff matrix – cartilage and bone – contribute to the skeletal elements of the head (reviewed by Kaucka, 2019). Although the majority of the skull is formed by bone postnatally, the development, growth and shaping of the skull in utero is dependent on the cartilage that represents the primary template of facial shape. Recently, we have discovered major principles of the growth and shaping of the mammalian embryonic face that filled in long standing gap in the field of craniofacial development (Kaucka, 2017).

Interestingly, we have noticed that the very first facial shape is established already before the existence of the cartilage, more specifically at the stage of mesenchymal condensations. Condensations are areas of soft tissue where mesenchymal cells have high proliferation rate. This brought up a key question: what are the molecular signals and their sources that instruct the formation of mesenchymal condensation and lay the basis of the future skeletal geometry and facial individuality.

Project #1: uncovering the gene regulatory network driving the induction of mesenchymal condensations.

The goal of this project is to reveal the molecular mechanisms underlying the formation of the very first facial shape. We are also interested in the regulation of gene expression (e.g. by enhancers) that is presumably the basis of the facial shape variability among distinct species. The successful applicant will utilize state-of-the-art techniques of single cell transcriptomics, single cell ATAC-seq (open chromatin analysis; to identify enhancers; 3C-technology), multicolor reporter genetic tracing in mouse, multiplex fluorescent in situ hybridization, immunohistochemistry, CRISPR/Cas9 and others to dissect the cellular and molecular machinery driving the establishment of the primary facial shape.

More than one third of all congenital abnormalities are represented by some craniofacial malformation, ranging from relatively mild changes of facial features or symmetry, through cleft lift, cleft palate or craniosynostoses, to very severe conditions affecting both feeding, breathing and overall survival. Interestingly, human craniofacial syndromes are often accompanied by other symptoms or disorders affecting the central nervous system or the sensory organs (reviewed by Marcucio, 2011). This suggests a link between the development of the nervous system and the formation of chondrocranium. Furthermore, in our recent work we discovered that one of the key signaling molecules of embryonic development, Sonic Hedgehog (Shh), is released in a spatiotemporal manner from both the developing brain and the forming olfactory organ (Kaucka, 2018). The ablation of Shh from a distinct parts of the central nervous system (CNS) or the ablation of the olfactory placode, led to the absence of different parts of chondrocranium. Our work proved that the chondrocranium is a composite structure induced by signals released in a precise spatio-temporal manner from distinct signaling centers located within the developing nervous system.

Project #2: Spatio-temporal mapping of the signaling centers inducing the skull

We aim to elaborate this new concept of signaling centers inside the developing nervous system and their importance for the formation of the individual bone elements and integration of these bones into a complex skull. The goal is to investigate the spatio-temporal existence and effect of major instructing signals across several animal species (mouse, chicken, zebrafish, Xenopus and others) and shed a new light on the bone homology and the evolutionary basis of facial variability. Successful candidate will combine transcriptomics data to uncover signals with the potential to induce the formation of condensation, cartilage or bone and use novel fluorescent in situ hybridization methods and immunohistochemistry to map them in 3D space. Further validation will require candidate gene tissue-and time-specific knockout performed in vivo.

Project #3: Co-evolution of the skull and the postcranial skeleton

The aim of this study is to understand the genetic basis of vertebrate skeleton diversity. We want to understand the relationship between the formation of the skull and postcranial skeleton. These two skeletal compartments represent an adaptation to the various feeding strategies (feeding apparatus in fishes, beak in birds, hyperkinetic skull in snakes, adaptations to the herbivorous and carnivorous, chewing and filtering in mammals) or different types of locomotion (quadrupedal, flying, undulation and swimming) across vertebrates. We observed a correlation between the bauplan of these two units and aim to dissect the genetic mechanisms of the diversification of the vertebrate skeleton.

We offer stimulating and friendly environment, interdisciplinary expertise, state-of-the-art techniques (genetic tracing, CRISPR/Cas9 knockouts performed in house, novel staining methods, broad spectrum of sequencing possibilities, bioinformatical support etc), various animal models, support in developing own ideas, frequent discussions and being a valuable part of an international team.

We encourage the IMPRS applicants with the interest in our research projects to contact us for more details (kaucka@evolbio.mpg.de) or to discuss more research directions available in our laboratory.

For more information on our research directions:

  1. Spatiotemporal structure of cell fate decisions in murine neural crest. Science, 2019
    https://science.sciencemag.org/content/364/6444/eaas9536.long
  2. Signals from the brain and olfactory epithelium control shaping of the mammalian nasal capsule cartilage. eLife 2018
    https://elifesciences.org/articles/34465
  3. Oriented clonal cell dynamics enables accurate growth and shaping of vertebrate cartilage. eLife 2017
    https://elifesciences.org/articles/25902
  4. Analysis of neural crest-derived clones reveals novel aspects of facial development. Science Advances 2016.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972470/

Review: Evolution and development of the cartilaginous skull: From a lancelet towards a human face. SCDB, 2019, https://www.sciencedirect.com/science/article/pii/S1084952117301453?via%3Dihub

For a complete reference list see:
https://www.ncbi.nlm.nih.gov/pubmed/?term=Kaucka%20M%5BAuthor%5D&cauthor=true&cauthor_uid=31710038

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