R e s e a r c h 

Developmental patterning and Notch-Delta signaling

I am interested in symmetry breaking and the emergence of patterns during development. Notch signaling is a highly conserved signaling pathway that plays a fundamental role in a plethora of processes including cell differentiation during the development and adult life of multicellular organisms. Notch signaling is a form of cell-cell communication, takes place locally between cells that are in direct contact with one another, and can lead to the self-organization of spatial patterns.

 

I have worked closely with experimental collaborators to study the role of Notch signaling in the development of the Drosophila fly notum. We have shown that, in this system, Notch signaling acts like a developmental clock and is important for timely and robust pattern formation.

 

I am also interested in the ways in which contact mediated signaling can lead to pattern formation, particularly when cells can reach one another at a distance through cellular protrusions. My recent work in collaboration with the Clarke and Alexandre groups has shown that spatiotemporal patterns of neuronal differentiation in the zebrafish spinal cord are controlled by Notch signalling mediated by transient protrusions. 

 

Collaborators: Buzz Baum, Paula Alexandre, Jon Clarke.

 

Key publications:

  • Hadjivasiliou Z, Moore R, McIntosh B, Clarke J, and Alexandre P,  2019 Basal protrusions mediate spatiotemporal patterns of spinal neuron differentiation. Dev Cell, 49, 907-919

  • Hunter GL, Hadjivasiliou Z, Bonin H, He L, Perrimon N, Charras G, and Baum B, 2016 Coordinated control of Notch-Delta signalling and cell division aids lateral inhibition mediated tissue patterning, Development, 143, 2305-2310


  • Hadjivasiliou Z, Hunter GL, and Baum B, 2016 A new mechanism for spatial pattern generation via lateral and protrusion-mediated lateral inhibition, J R Soc Interface, 13, 20160484


Growth control and scaling of morphogen gradients

Morphogens are secreted factors that form graded concentration profiles in developing tissues through diffusion and degradation. Patterning emerges when cells activate different target genes as a function of the morphogen concentration that they sense. At the same time, morphogen signalling controls tissue and organismal growth. I am interested in this coupling between growth and patterning and its implications in the development and  evolution of animal body plans.

 

Morphological structures can adapt to size as an organism grows. This is often attributed to the adaptation or scaling of the morphogen profile to the new tissue size. I am developing theoretical models based on physical principles to understand how morphogen scaling occurs during development. I have also developed statistical tools that allow us to quantify the transport kinetics of the morphogen and growth factor Dpp in the developing wing of the fruitfly, and assess how the processes through which morphogens move in tissues adapt during growth. 

 

Collaborators: Frank Jülicher, Marcos Gonzalez-Gaitan, Maria Romanova-Michaelides,  Daniel Aguilar-Hidalgo.

Upcoming publications:

  • Aguilar-Hidalgo D, Hadjivasiliou Z, Romanova-Michaelides M, Gonzalez-Gaitan M and Jülicher F, Dynamics modes of morphogen transport, arXiv:1909.13280 

  • Romanova-Michaelides M, Hadjivasiliou Z, Aguilar-Hidalgo D, Basagiannis D, Seum C, Dubois M, Julicher F, & Gonzalez-Gaitan M, Morphogen gradient scaling through recycling of intracelular Dpp, Under Review

Mating type evolution

 

Sex requires the fusion of two cells. Mating gametes (sexual cells) are rarely the same, exhibiting some form of morphological, functional or genetic difference. This pattern extends to isogamous species whose gametes lack any sort of morphological or behavioral asymmetry yet posses self-incompatible gametes. In this case, gamete identity is determined genetically at the mating type locus. Why should species whose gametes look and behave in the same way evolve mating types? What specifies the number of mating types, which can vary from two up to several thousand? Why do some unicellular species such as yeasts and many ciliates determine their mating type identity stochastically? And how can the evolution of the mating type locus help us understand how sex chromosomes, anisogamy and sexes have evolved? My research addresses these questions using tools and concepts from evolutionary theory, genetics and physics.

 

Collaborators: Andrew Pomiankowski, Nick Lane, Bram Kuijper, Yoh Iwasa.

 

Key publications:

  • Hadjivasiliou Z, and Pomiankowski A , 2019 Evolution of the mating type locus with suppressed recombination. eLife, 8, e48239.

  • Hadjivasiliou Z, and Pomiankowski A, 2016 Gamete signalling underlies the evolution of two and multiple mating types, Phil Trans B, 371, 20150531

  • Hadjivasiliou Z, Pomiankowski A, and Kuijiper B, 2016 The evolution of mating type switching, Evolution, 70, 1569-1581


  • Hadjivasiliou Z, Iwasa Y, and Pomiankowski A, 2015 Cell-cell signalling in sexual chemotaxis: A basis for gametic differentiation, mating types and sexes, J R Soc Interface, 12, 20150342


Mitochondrial inheritance

 

We inherit our mother’s mitochondria and so do most multicellular organisms. Uniparental inheritance of mitochondria is also common amongst unicellular organisms. Why is this pattern of inheritance so widespread? And what can we infer about the evolution of mating types or speciation through the lens of the mitochondrial genome and its inheritance patterns? I am interested in addressing these questions both by developing new theory and by working with experimentalists that study mitochondrial genetics.

 

Collaborators:  Andrew Pomiankowski, Nick Lane, Dan Mishmar.

 

Key publications:

  • Radzvilavicius AL, Hadjivasiliou Z, Pomiankowski A, and Lane N, 2016 Selection for mitochondrial quality drives the evolution of germline, PLoS Biology, 14, e2000410


  • Yaacov DB, Hadjivasiliou Z, Levin L, Zarivach R, Bouskila A, and Mishmar D, 2015
Mitochondria involvement in vertebrate speciation? The case of mito-nuclear genetic divergence in chameleons, Genome Biol Evol, 7, 3322-3336


  • Hadjivasiliou Z, Lane N, Seymour RM, and Pomiankowski A, 2013 Dynamics of mitochondrial inheritance in the evolution of binary mating types and two sexes. Proc R Soc B 280, 20131920