Fetal and postnatal neocortical development in a non-domesticated precocial ungulate, the European Wild Boar (Sus scrofa, LINNAEUS 1785)

• Applicant: Professorin Dr. Petra Wahle
• Subject Area: Developmental Neurobiology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 451084183

The current concepts of early neocortical development in mammals are largely based on data obtained in altricially born species such as small rodents (mouse, rat), more rarely carnivores (cat, ferret), and primates (monkey, human). Almost no information is available on ungulates which are precocial and born with nearly mature sensory and motor abilities. Moreover, the laboratory rodent lines are highly inbred and no longer wildtype. Here we propose to analyze fetal and postnatal neocortical development of the pig. The pig is an emerging model for translational research into heart, immunology, skin, cancer, and – since transgenesis is established in pig – meanwhile for many human neurodegenerative and metabolic disorders. This contrasts with surprisingly little knowledge at the cellular and neurochemical level of pig brain. From own preliminary published and ongoing work we already learned that many processes which in altricially born rodent and carnivore occur after birth and concurr in time with e.g. eye opening, proceed already during the fetal period in pig. We propose a thorough and comprehensive analysis of the following aspects of early brain development starting from the stage of cortical plate formation (E35, gestation in boar is 114 days) and well into postnatal stages: 1) delineation and fate of embryonic and fetal laminar compartments using immunohistochemistry with markers for proliferating cells, subplate neurons, cortical plate layers, and the Cajal-Retzius cells and interneurons of the marginal zone/layer I; 2) maturation of the inhibitory interneuron types and pyramidal cells of the cortical plate with an emphasis on axosomatic and axoaxonic innervations; 3) development of neuroglia, myelination, microglia and blood vessels in the laminar compartments; 4) profiling the expression of pre- and postsynaptic proteins using Western blot, aiming at aligning "synaptic age" in pig to rodent, carnivore, and human; 5) considering proteins and lectins the expression of which has been reported to correlate with onset and closure of the critical period of cortical plasticity in visual and somatosensory cortex. The project will be done with material from European wild boar, Sus scrofa (LINNAEUS 1785), a non-domesticated animal. Together, our goal is to introduce ungulate brain development to the field of corticogenesis and to promote other models for cortex development which may be closer to human than lissencephalic small rodents. Ultimately - from the forest to the lab – we feel that is high time to explore novel models in neurobiology.

• DFG Programme: Research Grants